Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish

Takashi Sugimura; Keiji Wakabayashi; Hitoshi Nakagama; Minako Nagao

doi:10.1111/j.1349-7006.2004.tb03205.x

. 2005 Aug 19;95(4):290–299. doi: 10.1111/j.1349-7006.2004.tb03205.x

Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish

Takashi Sugimura ^1,^✉, Keiji Wakabayashi ¹, Hitoshi Nakagama ¹, Minako Nagao ¹

PMCID: PMC11159436 PMID: 15072585

Abstract

Research leading to the discovery of a series of mutagenic and carcinogenic heterocyclic amines (HCAs) was inspired by the idea that smoke produced during cooking of food, especially meat or fish, might be carcinogenic. More than ten kinds of HCAs, actually produced by cooking or heating of meat or fish, have now been isolated and their structures determined, most being previously unregistered compounds. They are highly mutagenic towards Salmonella typhimurium in the presence of S9 mix and are also mutagenic in vitro and in vivo toward mammalian cells. HCAs have now been chemically synthesized in quantity and subjected to long‐term animal testing. When HCAs were fed in the diet, rodents developed cancers in many organs, including the colon, breast and prostate, and one HCA produced hepatomas in monkeys. The lesions exhibited alteration in genes including Apc, β‐catenin and Ha‐ras, and these changes provide clues to the induction mechanisms. The HCAs are oxidized to hydroxyamino derivatives by cytochrome P450s, and further converted to ester forms by acetyltransferase and sulfotransferase. Eventually, they produce DNA adducts through the formation of N‐C bonds at guanine bases. There are HCA‐sensitive and resistant strains of rodents and a search for the responsible genes is now under way. While the content of HCAs in dishes consumed in ordinary life is low and not sufficient in itself to explain human cancer, the coexistence of many other mutagens/carcinogens of either autobiotic or xenobiotic type and the possibility that HCAs induce genomic instability and heightened sensitivity to tumor promoters suggest that avoidance of exposure to HCAs or reduction of HCAs’biological effects as far as possible are to be highly recommended. Usage of microwave ovens for cooking and supplementation of the diet, for example with soy‐isoflavones, which have been found to suppress the occurrence of HCA‐induced breast cancers, should be encouraged. Advice to the general public about how to reduce the carcinogenic load imposed by HCAs would be an important contribution to cancer prevention.

References

1. Furth J, Lorenz E. Carcinogenesis by ionizing radiations. In: Hollaender A, editor. Radiation Biology. vol 1. New York : McGraw‐Hill; 1954. p. 1145. [Google Scholar]
2. Pott P. Chirurgical observations relative to the cataract, the polyps of the nose, the cancer of the scrotum, the different kinds of ruptures, and the mortification of the toes and feet. London : Hawes, Clarke and Collins; 1775. [Google Scholar]
3. Rehn L. Biasengeschwülste bei Fuchsin‐Arbeitern. Arch Klin Chir 1895; 50: 588–600. [Google Scholar]
4. Härting GH, Hesse W. Der Lungenkrebs, die Bergkrankheit in den Schneeberger Gruben. Vrtijschr gerlichtl Med 1879; 30: 296–309and 31: 102–32. [Google Scholar]
5. Spirtas R, Kaminski R. Angiosarcoma of the liver in vinyl chloride/polyvinyl chloride workers. Update of the NIOSH Register. J Occup Med 1977; 20: 427–9. [PubMed] [Google Scholar]
6. Friend SH, Bernards R, Rogeij S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323: 643–6. [DOI] [PubMed] [Google Scholar]
7. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991; 253: 665–9. [DOI] [PubMed] [Google Scholar]
8. Miki Y, Swensen J, Shattuck‐Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266: 66–71. [DOI] [PubMed] [Google Scholar]
9. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378: 762–3. [DOI] [PubMed] [Google Scholar]
10. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE. E‐Cadherin germline mutations in familial gastric cancer. Nature 1998; 26: 402–5. [DOI] [PubMed] [Google Scholar]
11. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000; 343: 78–85. [DOI] [PubMed] [Google Scholar]
12. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 1981; 66: 1191–308. [PubMed] [Google Scholar]
13. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001; 2: 533–43. [DOI] [PubMed] [Google Scholar]
14. McCann J, Ames BN. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci USA 1976; 73: 950–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
15. Sugimura T, Sato S, Nagao M, Yahagi T, Matsushima T, Seino Y, Takeuchi M, Kawachi T. Overlapping of carcinogens and mutagens. In: Magee PN, Takayama S, Sugimura T, Matushima T, editors. Fundamentals in cancer prevention. Tokyo : Univ Tokyo Press/Baltimore: Univ Park Press; 1976. p. 191–215. [Google Scholar]
16. Nagao M, Sugimura T, Matsushima T. Environmental mutagens and carcinogens. Annu Rev Genet 1978; 12: 117–59. [DOI] [PubMed] [Google Scholar]
17. Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. Salmonella mutagenicity tests. V. Results from the testing of 311 chemicals. Environ Mol Mutagen 1992; 19 Suppl 21: 2–141. [DOI] [PubMed] [Google Scholar]
18. IARC monographs on the evaluation of carcinogenic risks to humans. Overall evaluations of carcinogenicity: An updating of IARC monographs volumes 1 to 42. IARC monographs supplement 7. Lyon : IARC; 1987. p. 83–7. [PubMed] [Google Scholar]
19. van Egmond HP, Dekker WH. Worldwide regulations for mycotoxins and phycotoxins in Rome, Italy. 1996 (May 2731). The 9th IUPAC International Symposium on Mycotoxins and Phycotoxins.
20. Laqueur GL. Carcinogenic effects of cycad meal and cycasin, methyl‐azoxymethanol glycoside, in rats and effects of cycasin in germ free rats. Fed Proc 1964; 23: 1386–8. [PubMed] [Google Scholar]
21. Evans IA, Mason J. Carcinogenic activity of bracken. Nature 1965; 208: 913–4. [DOI] [PubMed] [Google Scholar]
22. van der Hoven JC, Aquilide A. A new mutagenic compound isolated from bracken fern (Pteridium aquilinum (L.) Kuhn). Carcinogenesis 1983; 4: 1587–90. [DOI] [PubMed] [Google Scholar]
23. Kondo S, Ichikawa‐Ryo H. Testing and classification of mutagenicity of furylfuramide in Escherichi coli. Jpn J Genet 1973; 48: 295–300. [Google Scholar]
24. Kada T. Escherichia coli mutagenicity of furylfuramide, Jpn J Genet 1973; 48: 301–5. [Google Scholar]
25. Yahagi T, Matsushima T, Nagao M, Seino Y, Sugimura T, Bryan GT. Mutagenicity of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid. Mutat Res 1976; 40: 9–14. [DOI] [PubMed] [Google Scholar]
26. Ikeda Y, Horiuchi S, Furuya T, Uchida O, Suzuki K, Azegami J. Induction of gastric tumors in mice by feeding of furylfuramide. Food Sanitation Study Council 1974; Ministry of Health and Welfare, Japan . [Google Scholar]
27. Sano T, Kawachi T, Matsukura N, Sasajima K, Sugimura T. Carcinogenicity of food additive, AF‐2, in hamsters and mice. Z Krebsforsch 1977; 89: 61–8. [DOI] [PubMed] [Google Scholar]
28. Sugimura T, Nagao M, Kawachi T, Honda M, Yahagi T, Seino Y, Sato S, Matsukura N, Matsushima T, Shirai A, Sawamura M, Matsumoto H. Mutagen‐car‐cinogens in foods with special reference to highly mutagenic pyrolytic products in broiled foods. In: Hiatt HH, Watson JD, Winsten JA, editors. Origins of human cancer. New York : Cold Spring Harbor; 1977. p. 1561–77. [Google Scholar]
29. Nagao M, Honda M, Seino Y, Yahagi T, Sugimura T. Mutagenicities of smoke condensates and the charred surface of fish and meat. Cancer Lett 1977; 2: 221–6. [DOI] [PubMed] [Google Scholar]
30. Commoner B, Vithayathil AJ, Dolora P, Nair S, Madyastha P, Cuca GC. Formation of mutagens in beef and beef extract during cooking. Science 1978; 201: 913–6. [DOI] [PubMed] [Google Scholar]
31. Sugimura T, Kawachi T, Nagao M, Yahagi T, Seino Y, Okamoto T, Shudo K, Kosuge T, Wakabayashi K, Iitaka T, Itai A. Mutagenic principle(s) in tryptophan and phenylalanine pyrolysis products. Proc Jpn Acad 1977; 53: 58–61. [Google Scholar]
32. Yamamoto T, Tsuji K, Kosuge T, Okamoto T, Shudo K, Takeda K, Iitaka K, Yamaguchi K, Seino Y, Yahagi T, Nagao M, Sugimura T. Isolation and structure determination of mutagenic substances in L‐glutamic acid pyrolysate. Proc Jpn Acad 1978; 54B: 248–50. [Google Scholar]
33. Yoshida D, Matsumoto T, Yoshimura R, Matsuzaki T. Mutagencity of amino‐α‐carboline in pyrolysis products of soybean globulin. Biochem Biophys Res Commun 1978; 83: 915–20. [DOI] [PubMed] [Google Scholar]
34. Spingarn NE, Kasai H, Vuolo LL, Nishimura S, Yamaizumi Z, Sugimura T, Matsushima T, Weisburger JH. Formation of mutagens in cooked foods. III. Isolation of potent mutagens from beef. Cancer Lett 1980; 9: 177–83. [DOI] [PubMed] [Google Scholar]
35. Wakabayashi K, Nagao M, Esumi H, Sugimura T. Food‐derived mutagens and carcinogens. Cancer Res 1992; 52 Suppl: 2092s–8s. [PubMed] [Google Scholar]
36. Kasai H, Yamaizumi Z, Wakabayashi K, Nagao M, Sugimura T, Tokoyama S, Miyazawa T, Spingrn NE, Weisburger JH, Nishimura S. Potent novel mutagens produced by broiling fish under normal conditions. Proc Jpn Acad 1980; 56B: 278–83. [Google Scholar]
37. Kasai H, Yamaizumi Z, Wakabayashi K, Nagao M, Sugimura T, Yokoyama S, Miyazawa T, Nishimura T. Structure and chemical synthesis of MeIQ, a potent mutagen isolated from broiled fish. Chem Lett 1980; 1391–4. [Google Scholar]
38. Kasai H, Yamaizumi Z, Shiomi T, Yokoyama S, Miyazawa T, Wakabayashi K, Nagao M, Sugimura T, Nishimura S. Structure of a potent mutagen isolated from fried beef. Chem Lett 1981; 485–8. [Google Scholar]
39. Felton JS, Knize MG, Shen NH, Lewis PR, Andresen BD, Happe J, Hatch FT. The isolation and identification of a new mutagen from fried ground beef: 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) Carcinogenesis 1986; 7: 1081–6. [DOI] [PubMed] [Google Scholar]
40. Tsuda M, Negishi C, Makino R, Sato S, Yamaizumi Z, Hirayama T, Sugimura T. Use of nitrite and hypochlorite treatments in determination of the contributions of IQ‐type and non‐IQ‐type heterocyclic amines to the mutagenicities in crude pyrolyzed materials, Mutat Res 1985; 147: 335–41. [DOI] [PubMed] [Google Scholar]
41. Jägerstad M, Lase Reutersward A, Olsson R, Grivas S, Nyhammar T, Olsson K, Dahlqvist A. Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds: effects of various amino acids. Food Chem 1983; 12: 239–44. [Google Scholar]
42. Felton JS, Jägerstad M, Knize MG, Skog K, Wakabayashi K. Contents in foods, beverages and tobacco. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 31–71. [Google Scholar]
43. Nagao M. Mutagenicity. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 163–95. [Google Scholar]
44. Terada M, Nagao M, Nakayasu M, Sakamoto H, Nakasato F, Sugimura T. Mutagenic activities of herterocyclic amines in Chinese hamster lung cells in culture. Environ Health Perspect 1986; 67: 117–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
45. Thompson LH, Tucker JD, Stewart SA, Christense ML, Salazar EP, Carrano AV, Felton JS. Genotoxicity of compounds from cooked beef in repair‐deficient CHO cells versus Salmonella mutagenicity. Mutagenesis 1987; 2: 483–7. [DOI] [PubMed] [Google Scholar]
46. Nagao M. A new approach to risk estimation of food‐borne carcinogens‐heterocyclic amines‐based on molecular information. Mutat Res 1999; 431: 3–12. [DOI] [PubMed] [Google Scholar]
47. Okochi E, Watanabe N, Shimada Y, Takahashi S, Wakazono K, Shirai T, Sugimura T, Nagao M, Ushijima T. Preferential induction of guanine deletion at 5′‐GGGA‐3′ in rat mammary glands by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Carcinogenesis 1999; 20: 1933–8. [DOI] [PubMed] [Google Scholar]
48. Okonogi H, Ushijima T, Zhang XB, Heddle JA, Suzuki T, Sofuni T, Felton JS, Ticker JD, Sugimura T, Nagao M. Agreement of mutational characteristics of heterocyclic amines in lacI of the Big Blue^® mouse with those in tumor related genes in rodents. Carcinogenesis 1997; 18: 745–8. [DOI] [PubMed] [Google Scholar]
49. Nagao M, Ushijma T, Toyota M, Inoue R, Sugimura T. Genetic changes induced by heterocyclic amines. Mutat Res 1997; 376: 161–7. [DOI] [PubMed] [Google Scholar]
50. Burnouf DY, Miturski R, Nagao M, Nakagama H, Nothisen M, Wagner J, Fuchs RPP. Early detection of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced mutations within the Apc gene of rat colon. Carcinogenesis 2001; 22: 329–35. [DOI] [PubMed] [Google Scholar]
51. Nagao M. A new approach to risk estimation of food‐borne carcinogens—heterocyclic amines—based on molecular information. Mutat Res 1999; 431: 3–12. [DOI] [PubMed] [Google Scholar]
52. Matsukura N, Kawachi T, Morino K, Ohgaki H, Sugimura T, Takayama S. Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolysate. Science 1981; 213: 346–7. [DOI] [PubMed] [Google Scholar]
53. Ohgaki H, Matsukura N, Morino K, Kawachi T, Sugimura T, Takayama S. Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates. Carcinogenesis 1984; 5: 815–9. [DOI] [PubMed] [Google Scholar]
54. Ohgaki H, Kusama K, Matsukura N, Morino K, Hasegawa H, Sato S, Takayama S, Sugimura T. Carcinogenicity in mice of a mutagenic compound, 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, from broiled sardine, cooked beef and beef extract. Carcinogenesis 1984; 5: 921–4. [DOI] [PubMed] [Google Scholar]
55. Ohgaki H, Hasegawa H, Suenaga M, Sato S, Takayama S, Sugimura T. Induction of hepatocellular carcinoma and highly metastatic squamous cell carcinomas in the forestomach of mice by feeding 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoline. Carcinogenesis 1986; 7: 1889–93. [DOI] [PubMed] [Google Scholar]
56. Ohgaki H, Hasegawa H, Suenaga M, Sato S, Takayama S, Sugimura T. Carcinogenicity in mice of a mutagenic compound, 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) from cooked foods. Carcinogenesis 1987; 8: 665–8. [DOI] [PubMed] [Google Scholar]
57. Fujita H, Nagano K, Ochiai M, Ushijima T, Sugimura T, Nagao M, Matsushima T. Difference in target organs in carcinogenesis with a heterocyclic amine, 2‐amino‐3,4‐dimethylimido[4,5‐f]quinoline, in different strains of mice. Jpn J Cancer Res 1999; 90: 1203–6. [DOI] [PMC free article] [PubMed] [Google Scholar]
58. Esumi H, Ohgaki H, Kohzen E, Takayama S, Sugimura T. Induction of lymphoma in CDF1 mice by the food mutagen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Jpn J Cancer Res 1989; 80: 1176–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
59. Takayama S, Nakatsuru Y, Ohagaki H, Sato S, Sugimura T. Carcinogenicity in rats of a mutagenic compound, 3‐amino‐1,4‐dimethyl‐5H‐pyrido[4,3‐b]indole from tryptophan pyrolsate. Jpn J Cancer Res 1985; 76: 815–7. [PubMed] [Google Scholar]
60. Takahashi M, Toyoda K, Aze Y, Furuta K, Mitsumori K, Hayashi Y. The rat urinary bladder as a new target of heterocyclic amine carcinogenicity: tumor induc‐tionby 3‐amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole acetate. Jpn J cancer Res 1993; 84: 852–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
61. Takayama S, Masuda M, Mogami M, Ohgaki H, Sato S, Sugimura T. Induction of cancers in the intestine, liver and various other organs of rats by feeding mutagens from glutamic acid pyrolysate. Gann 1984; 75: 207–13. [PubMed] [Google Scholar]
62. Tamano S, Hasegawa R, Hagiwara A, Nagao M, Sugimura T, Ito N. Carcinogenicity of a mutagenic compound from food, 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole (MeAαC), in male F344 rats. Carcinogenesis 1994; 15: 2009–15. [DOI] [PubMed] [Google Scholar]
63. Takayama S, Nakatsuru Y, Masuda M, Ohgaki H, Sato S, Sugimura T. Demonstration of carcinogenicity in F344 rats of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline from broiled sardine, fried beef and beef extract. Gann 1984; 75: 467–70. [PubMed] [Google Scholar]
64. Kato T, Migita H, Ohgaki H, Sato S, Takayama S, Sugimura T. Induction of tumors in the Zymbal gland, oral cavity, colon, skin and mammary gland of F344 rats by a mutagenic compound, 2‐amino‐3,4‐dimethylimidazo[4,5‐f]quinoline. Carcinogenesis 1989; 10: 601–3. [DOI] [PubMed] [Google Scholar]
65. Kato T, Ohgaki H, Hasegawa H, Sato S, Takayama S, Sugimura T. Carcinogenicity in rats of a mutagenic compound, 2‐amino‐3,8‐dimethylimi‐dazo[4,5‐f]quinoxaline. Carcinogenesis 1988; 9: 71–3. [DOI] [PubMed] [Google Scholar]
66. Ito N, Hasegawa R, Sano M, Tamano S, Esumi H, Takayama S, Sugimura T. A new colon and mammary carcinogen in cooked food, 2‐amino‐1‐methyl‐6‐phe‐nylimidazo[4,5‐b]pyridine (PhIP). Carcinogenesis 1991; 12: 1503–6. [DOI] [PubMed] [Google Scholar]
67. Shirai T, Sano M, Tamano S, Takahashi S, Hirose M, Futakuchi M, Hasegawa R, Imaida K, Matsumoto K, Wakabayashi K, Sugimura T, Ito N. The prostate: a target for carcinogenicity of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) derived from cooked foods. Cancer Res 1997; 57: 195–8. [PubMed] [Google Scholar]
68. Ochiai M, Imai H, Sugimura T, Nagao M, Nakagama H. Induction of intestinal tumors and lymphomas in C57BL/6N mice by a food‐borne carcinogen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Jpn J Cancer Res 2002; 93: 478–83. [DOI] [PMC free article] [PubMed] [Google Scholar]
69. Takayama S, Nakatsuru Y, Ohgaki H, Sato S, Sugimura T. Atrophy of salivary glands and pancreas of rats fed on diet with amino‐methyl‐α‐carboline. Proc Jpn Acad 1985; 61 Ser B: 277–80. [Google Scholar]
70. Tanaka T, Barnes WS, Williams GM, Weisburger JH. Multipotential carcinogenicity of the fried food mutagen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in rats. Gann 1985; 76: 570–6. [PubMed] [Google Scholar]
71. Adamson RH, Thorgeirsson UP, Snyderwine EG, Thorgeirsson SS, Reeves J, Dalgard DW, Takayama S, Sugimura T. Carcinogenicity of 2‐amino‐3‐methylimi‐dazo[4,5‐f]quinoline in nonhuman primates: induction of tumors in three macaques. Jpn J Cancer Res 1990; 81: 10–4. [DOI] [PMC free article] [PubMed] [Google Scholar]
72. Yamazoe Y, Shimada M, Kamataki T, Kato R. Microsomal activation of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate. Cancer Res 1983; 43: 5768–74. [PubMed] [Google Scholar]
73. Shimada T, Guengerich FP. Activation of amino‐α‐carboline, 2‐amino‐1‐methyl‐6‐phenyimidazo[4,5‐b]pyridine, and a copper phthalocyanine cellulose extract of cigarette smoke condensate by cytochrome P‐450 enzymes in rat and human liver microsomes. Cancer Res 1991; 56: 2979–84. [PubMed] [Google Scholar]
74. Hammons GJ, Miton D, Stepps K, Guengerrich FP, Tukey RH, Kadlubar FF. Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes. Carcinogenesis 1997; 18: 851–4. [DOI] [PubMed] [Google Scholar]
75. Turesky R, Constable A, Fay LB, Guengerich FP. Interspecies differences in metabolism of heterocyclic amines by rat and human P450 1A2. Cancer Lett 1999; 143: 109–12. [DOI] [PubMed] [Google Scholar]
76. Hickman D, Pope J, Patil S, Fakis G, Smelt V, Stanley L, Payton M, Unadkat J, Sim E. Expression of arylamine N‐acetyltransferase in human intestine. Gut 1998; 42: 402–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
77. Hein DW, Doll MA, Rustan TD, Gray K, Feng Y, Ferguson RJ, Grant DM. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 1993; 14: 1633–8. [DOI] [PubMed] [Google Scholar]
78. Minchin RF, Reeves PT, Teitel CH, McManus ME, Mojarrabi B, Illett KF, Kadlubar FF. N‐and O‐acetylation of aromatic and HCA carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS‐1 cells. Biochem Biophys Res Commun 1992; 185: 839–44. [DOI] [PubMed] [Google Scholar]
79. LeMarchand L, Hankin JH, Pierce LM, Sinha R, Nerurkar PV, Franke AA, Wilkens LR, Kolonel LN, Donlon T, Seifried A, Custer LJ, Lum‐Jones A, Chang W. Well‐done red meat, metabolic phenotypes and colorectal cancer in Hawaii. Mutat Res 2002; 506–507: 205–214. [DOI] [PubMed] [Google Scholar]
80. Ishibe N, Sinha R, Hein DW, Kulldorff M, Strickland P, Fretland AJ, Chow WH, Kadlubar FF, Lang NP, Rothman N. Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. Pharmacogenetics 2002; 12: 145–50. [DOI] [PubMed] [Google Scholar]
81. Snyderwine EG, Roller PP, Adamson RH, Sato S, Thorgeirsson SS. Reaction of N‐hydroxylamine and N‐acetoxy derivatives of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline with DNA. Synthesis and identification of N‐(deoxyguanosin‐8‐yl)‐IQ. Carcinogenesis 1988; 9: 1061–5. [DOI] [PubMed] [Google Scholar]
82. Nagaoka H, Wakabayashi K, Kim S‐B, Kim I‐S, Tanaka Y, Ochiai M, Tada A, Nukaya H, Sugimura T, Nagao M. Adduct formation at C‐8 of guanine on in vitro reaction of the ultimate form of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine with 2′‐deoxyguanosine and its phosphate esters. Jpn J Cancer Res 1992; 83: 1025–9. [DOI] [PMC free article] [PubMed] [Google Scholar]
83. Turesky RJ, Rossi SC, Welti D, Lay JO Jr, Kadlubar FF. Characterization of DNA adducts formed in vitro by reaction of N‐hydroxy‐2‐amino‐3‐methylimidazo[4,5‐f]quinoline and N‐hydroxy‐2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline at C‐8 and N² atoms of guanine. Chem Res Toxicol 1992; 5: 479–90. [DOI] [PubMed] [Google Scholar]
84. Brown K, Hingerty BE, Guenther EA, Krishnan VV, Broyde S, Turteltaub KW, Cosman M. Solution structure of the 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b] pyridine C8‐deoxyguanosine adduct in duplex DNA. Proc Natl Acad Sci USA 2001; 98: 8507–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
85. Tatemachi M, Nomura S, Ogura T, Sone H, Nagata H, Esumi H. Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia. Cancer Res 1999; 15: 3893–8. [PubMed] [Google Scholar]
86. Guy PA, Gremaud E, Richoz J, Turesky RJ. Quantitative analysis of mutagenic heterocyclic aromatic amines in cooked meat using liquid chromatography‐atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr A 2000; 883: 89–102. [DOI] [PubMed] [Google Scholar]
87. Kataoka H, Kajima KK. Analysis of heterocyclic amines as their N‐dimethylami‐nomethylene derivatives by gas chromatography with nitrogen‐phophorus selective detection. J Chromatogr A 1997; 767: 187–94. [Google Scholar]
88. Kataoka H, Nishioka S, Kobayashi M, Hanaoka T, Tsugane S. Analysis of mutagenic heterocyclic amines in cooked food samples by gas chromatography with nitrogen‐phosphorus detector. Bull Environ Contam Toxicol 2002; 69: 682–9. [DOI] [PubMed] [Google Scholar]
89. Felton JS, Knize MG, Salmon CP, Malfatti MA, Kulp KS. Human exposure to heterocyclic amine food mutagens/carcinogens: relevance to breast cancer. Environ Mol Mutagen 2002; 39: 112–8. [DOI] [PubMed] [Google Scholar]
90. Knize MG, Salmon CP, Felton JS. Mutagenic activity and heterocyclic amine carcinogens in commercial pet foods. Mutat Res 2003; 539: 195–201. [DOI] [PubMed] [Google Scholar]
91. Ushiyama H, Wakabayashi K, Hirose M, Ito H, Sugimura T, Nagao M. Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. Carcinogenesis 1991; 12: 1417–22. [DOI] [PubMed] [Google Scholar]
92. DeBruin LS, Martos PA, Josephy PD. Detection of PhIP (2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine) in the milk of healthy women. Chem Res Toxicol 2001; 14: 1523–8. [DOI] [PubMed] [Google Scholar]
93. Gorlewska‐Roberts K, Green B, Fares M, Ambrosone CB, Kadlbar FF. Carcinogen‐DNA adducts in human breast epithelial cells. Environ Mol Mutagen 2002; 39: 184–92. [DOI] [PubMed] [Google Scholar]
94. Takayama K, Yamashita K, Wakabayashi K, Sugimura T, Nagao M. DNA modification by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine in rats. Jpn J Cancer Res 1989; 80: 1145–8. [DOI] [PMC free article] [PubMed] [Google Scholar]
95. Skipper PL, Tannenbaum SR. Protein adducts in the molecular dosimetry of chemical carcinogens. Carcinogenesis 1990; 11: 507–18. [DOI] [PubMed] [Google Scholar]
96. Umemoto A, Monden Y, Tsuda M, Grivas S, Sugimura T. Oxidation of the 2‐hydroxyamino derivative of 2‐amino‐6‐methyldipyrido[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐1) to its 2‐nitroso form, an ultimate form reacting with hemoglobin thiol groups. Biochem Biophys Res Commun 1988; 151: 1326–31. [DOI] [PubMed] [Google Scholar]
97. Magagnotti C, Orsi F, Bagnati R, Celli N, Rotilio D, Fanelli R, Airoldi L. Effect of diet on serum albumin and hemoglobin adducts of 2‐amino‐1‐methyl‐6‐phenylim‐idazo[4,5‐b]pyridine (PhIP) in humans. Int J Cancer 2000; 88: 1–6. [DOI] [PubMed] [Google Scholar]
98. Nagao M, Yahagi T, Honda M, Seino Y, Matsushima T, Sugimura T. Demonstration of mutagenicity of aniline and o‐toluidine by norharman. Proc Jpn Acad 1977: 53: 34–7. [Google Scholar]
99. Totsuka Y, Hada N, Matsumoto K, Kawahara N, Murakami Y, Yokoyama Y, Sugimura T, Wakabayashi K. Structure determination of a mutagenic aminophenylnorharman produced by the co‐mutagen norharman with aniline. Carcinogenesis 1998; 19: 1995–2000. [DOI] [PubMed] [Google Scholar]
100. Totsuka Y, Kataoka H, Takamura‐Enya T, Kawahara N, Nishigaki R, Sugimura T, Wakabayashi K. Structure of DNA adduct formed with aminophenylnorharman, being responsible for the comutagenic action of norharman with aniline. Chem Res Toxicol 2002; 15: 1288–94. [DOI] [PubMed] [Google Scholar]
101. Totsuka Y, Kataoka H, Takamura‐Enya T, Sugimura T, Wakabayashi K. In vitro and in vivo formation of aminophenylnorharman from norharman and aniline. Mutat Res 2002; 506–507: 49–54. [DOI] [PubMed] [Google Scholar]
102. Sugimura T. A new concept of co‐mutagenicity from a phenomenon forgotten for the past two decades: is it more important than previously expected?; Environ Health Perspect 1998; 106: A522–3. [DOI] [PMC free article] [PubMed] [Google Scholar]
103. Sugimura T, Nagao M, Wakabayashi K. Complex factors pertinent to human hazard risk. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 349–59. [Google Scholar]
104. Rohrmann S, Becker N. Development of a short questionnaire to assess the dietary intake of heterocyclic aromatic amines. Public Health Nutr 2002; 5: 699–705. [DOI] [PubMed] [Google Scholar]
105. Nowell S, Coles B, Sinha R, Macleod S, Ratnasinghe DL, Stotts C, Kadlubar FF, Ambrosone CB, Lang NP. Analysis of total meat intake and exposure to individual heterocyclic amines in a case‐control study of colorectal cancer: contribution of metabolic variation to risk. Mutat Res 2002; 506–507: 175–85. [DOI] [PubMed] [Google Scholar]
106. Kobayashi M, Hanaoka T, Nishioka S, Kataoka H, Tsugane S. Estimation of dietary HCA intakes in a large‐scale population‐based prospective study in Japan. Mutat Res 2002; 506–507: 233–41. [DOI] [PubMed] [Google Scholar]
107. Hasegawa R, Tanaka H, Tamano S, Shirai T, Nagao M, Sugimura T, Ito N. Synergistic enhancement of small and large intestinal carcinogenesis by combined treatment of rats with five heterocyclic amines in a medium‐term multi‐organ bio‐assay. Carcinogenesis 1994; 15: 2567–73. [DOI] [PubMed] [Google Scholar]
108. Takahashi M, Furukawa F, Miyakawa Y, Sato H, Hasegawa R, Hayashi Y. 3‐Amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole initiates two‐stage carcinogenesis in mouse skin but is not a complete carcinogen. Jpn J Cancer Res 1986; 77: 509–13. [PubMed] [Google Scholar]
109. Nagao M, Ushijima T, Toyota M, Inoue R, Sugimura T. Genetic changes induced by heterocyclic amines. Mutat Res 1997; 376: 161–7. [DOI] [PubMed] [Google Scholar]
110. Dashwood RH, Suzui M, Nakagama H, Sugimura T, Nagao M. High frequency of β‐catenin (Ctnnb1) mutations in the colon tumors induced by two heterocyclic amines in the F344 rat. Cancer Res 1998; 58: 1127–9. [PubMed] [Google Scholar]
111. Yu M, Snyderwine EG. H‐ras oncogene mutations during development of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced rat mammary gland cancer. Carcinogenesis 2002; 23: 2123–8. [DOI] [PubMed] [Google Scholar]
112. Qiu C, Shan L, Yu M, Snyderwine EG. Deregulation of the cyclin D1/Cdk4 retin‐oblastoma pathway in rat mammary gland carcinomas induced by the food‐derived carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Cancer Res 2003; 63: 5674–8. [PubMed] [Google Scholar]
113. Watanabe N, Okochi E, Hirayama Y, Shimada Y, Yanagihara K, Yoshida MC, Takahashi S, Mochizuki M, Sugimura T, Nagao M, Ushijima T. Single nucleotide instability without microsatellite instability in rat mammary carcinomas. Cancer Res 2001; 61: 2632–40. [PubMed] [Google Scholar]
114. Okochi E, Watanabe N, Sugimura T, Ushijima T. Single nucleotide instability: a wide involvement in human and rat mammary carcinogenesis? Single nucleotide instability without microsatellite instability in rat mammary carcinomas. Mutat Res 2002; 506–507: 101–11. [DOI] [PubMed] [Google Scholar]
115. Ubagai T, Ochiai M, Kawamori T, Imai H, Sugimura T, Nagao M, Nakagama H. Efficient induction of rat large intestinal tumors with a new spectrum of mutations by intermittent administration of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyri‐dine in combination with a high fat diet. Carcinogenesis 2002; 23: 197–200. [DOI] [PubMed] [Google Scholar]
116. Ghoshal A, Preisegger KH, Takayama S, Thorgeirsson SS, Snyderwine EG. Induction of mammary tumors in female Sprague‐Dawley rats by the food‐derived carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine and effect of dietary fat. Carcinogenesis 1994; 15: 2429–33. [DOI] [PubMed] [Google Scholar]
117. Takahashi M, Totsuka Y, Masuda M, Fukuda K, Oguri A, Yazawa K, Sugimura T, Wakabayashi K. Reduction in formation of 2‐amino‐1‐methyl‐6‐phenylimi‐dazo[4,5‐b]pyridine (PhIP)‐induced aberrant crypt foci in the rat colon by docosa‐hexaenoic acid (DHA). Carcinogenesis 1997; 18: 1937–41. [DOI] [PubMed] [Google Scholar]
118. Liew C, Schut HAJ, Chin SF, Pariza MW, Dashwood RH. Protection of conjugated linoleic acids against 2‐amino‐3‐methylimidazo[4,5‐f]quinoline‐induced colon carcinogenesis in the F344 rats: a study of inhibitory mechanisms. Carcinogenesis 1995; 16: 3037–43. [DOI] [PubMed] [Google Scholar]
119. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 2003; 95: 906–13. [DOI] [PubMed] [Google Scholar]
120. Ohta T, Nakatsugi S, Watanabe K, Kawamori T, Ishikawa F, Morotomi M, Sugie S, Toda T, Sugimura T, Wakabayashi K. Inhibitory effects of Bifidobacterium‐fermented soy milk on 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine‐induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones. Carcinogenesis 2000; 21: 937–41. [DOI] [PubMed] [Google Scholar]
121. Hirose M, Hasegawa R, Kimura J, Akagi K, Yoshida Y, Tanaka H, Miki T, Satoh T, Wakabayashi K, Ito N, Shirai T. Inhibitory effects of 1‐O‐hexyl‐2,3,5‐trimethyl‐hydroquinone (HTHQ), green tea catechins and other antioxidants on 2‐amino‐6‐methyldipyrido[1,2‐a;3′,2′‐d]imidazole (Glu‐P‐1)‐induced rat hepatocarcinogenesis and dose‐dependent inhibition by HTHQ of lesion induction by Glu‐P‐1 or 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx). Carcinogenesis 1995; 16: 3049–55. [DOI] [PubMed] [Google Scholar]
122. Hirose M, Akagi K, Hasegawa R, Yaono M, Satoh T, Hara Y, Wakabayashi K, Ito N. Chemoprevention of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced mammary gland carcinogenesis by antioxidants in F344 female rats. Carcinogenesis 1995; 16: 217–21. [DOI] [PubMed] [Google Scholar]
123. Guo D, Schut HAJ, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Protection by chlorophyllin and indole‐3‐carbinol against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced DNA adducts and colonic aberrant crypts in the F344 rats. Carcinogenesis 1995; 16: 2931–7. [DOI] [PubMed] [Google Scholar]
124. Xu M, Bailey AC, Hernaez JF, Taoka CR, Schut HAJ, Dashwood RH. Protection by green tea, black tea, and indole‐3‐carbinol against 2‐amino‐3‐methylimi‐dazo[4,5‐f]quinoline‐induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis 1996; 17: 1429–34. [DOI] [PubMed] [Google Scholar]
125. Dashwood RH. Modulation of heterocyclic amine‐induced mutagenicity and carcinogenicity: an 'A‐to‐Z' guide to chemopreventive agents, promoters, and transgenic models. Mutat Res 2002; 11: 89–112. [DOI] [PubMed] [Google Scholar]
126. Tsuda H, Sekine K, Uehara N, Takasuka N, Moore MA, Konno Y, Nakashita K, Degawa M. Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rats. Cancer Lett 1999; 143: 229–34. [DOI] [PubMed] [Google Scholar]
127. Reddy BS, Rivenson A. Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, a food mutagen. Cancer Res 1993; 53: 3914–8. [PubMed] [Google Scholar]
128. Guo D, Horio DT, Grove JS, Dashwood RH. Inhibition by chlorophyllin of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline‐induced tumorigenesis in the male F344 rat. Cancer Lett 1995; 95: 161–5. [DOI] [PubMed] [Google Scholar]
129. Hasegawa R, Hirose M, Kato T, Hagiwara A, Boonyaphiphat P, Nagao M, Ito N, Shirai T. Inhibitory effect of chlorophyllin on PhIP‐induced mammary carcinogenesis in female F344 rats. Carcinogenesis 1995; 16: 2243–6. [DOI] [PubMed] [Google Scholar]
130. Ohgaki H, Kawachi T, Matsukura N, Morino K, Miyamoto M, Sugimura T. Genetic control of susceptibility of rats to gastric carcinoma. Cancer Res 1983; 43: 3663–7. [PubMed] [Google Scholar]
131. Ushijima T, Yamamoto M, Suzui M, Kuramoto T, Yoshida Y, Nomoto T, Tatematsu M, Sugimura T, Nagao M. Chromosomal mapping of genes controlling development, histological grade, depth of invasion, and size of rat stomach carcinomas. Cancer Res 2000; 60: 1092–6. [PubMed] [Google Scholar]
132. Demant P. Cancer susceptibility in the mouse: genetics, biology and implications for human cancer. Nat Rev 2003; 4: 721–34. [DOI] [PubMed] [Google Scholar]
133. Ruivenkamp CAL, van Wezel T, Zanon C, Stassen APM, Vlek C, Csikos T, Klous AM, Tripodis N, Perrakis A, Boerrigter L, Groot PC, Lindeman J, Mooi SK, Meijjer GA, Scholten G, Dauwerse H, Paces V, van Zandwijk N, van Ommen GJB, van Demant P. Ptprj is a candidate for the mouse colon‐cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet 2002; 31: 295–300. [DOI] [PubMed] [Google Scholar]
134. Dietrich WF, Lander ES, Smith JS, Moser AR, Gould KA, Luongo C, Borenstein N, Dove W. Genetic identification of Mom‐1, a major modifier locus affecting Min‐induced intestinal neoplasia in the mouse. Cell 1993; 75: 631–9. [DOI] [PubMed] [Google Scholar]
135. MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buchberg AM. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin‐induced intestinal neoplasia. Cell 1995; 81: 957–66. [DOI] [PubMed] [Google Scholar]
136. Ishiguro Y, Ochiai M, Sugimura T, Nagao M, Nakagama H. Strain differences of rats in the susceptibility to aberrant crypt foci formation by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine: no implication of Apc and Pla2g2a genetic polymorphisms in differential susceptibility. Carcinogenesis 1999; 20: 1063–8. [DOI] [PubMed] [Google Scholar]
137. Nakagama H, Souda K, Ochiai M, Ishiguro Y, Sugimura T, Nagao M. Genetic analysis of the susceptibility in rats to aberrant crypt foci formation by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine, PhIP. Cancer Lett 1999; 143: 205–9. [DOI] [PubMed] [Google Scholar]
138. Knize MG, Kulp KS, Salmon CP, Keating GA, Felton JS. Factors affecting human heterocyclic amine intake and the metabolism of PhIP. Mutat Res 2002; 506–507, 153–62. [DOI] [PubMed] [Google Scholar]
139. Persson E, Sjoholm I, Skog K. Effect of high water‐holding capacity on the formation of heterocyclic amines in fried beefburgers. J Agric Food Chem 2003; 51: 4472–7. [DOI] [PubMed] [Google Scholar]
140. Underwood A, Springen K, Davis A. Cancer & diet. Newsweek 1998; Nov 30: 42–8. [Google Scholar]
141. Salmon CP, Kinze MG, Panteleakos FN, Wu RW, Nelson DO, Felton JS. Minimization of heterocyclic amines and thermal inactivation of Escherichia coli in fried ground beef. J Natl Cancer Inst 2000; 92: 1773–8. [DOI] [PubMed] [Google Scholar]
142. O'Neil. Hamburger safety may be partly in the flip. The New York Times 2000; Dec 5. [Google Scholar]
143. Johansson M, Jägerstad M. Influence of edible oils and fatty acids on the formation of heterocyclic amines in a model system. Food Chem 1996; 56: 69–75. [DOI] [PubMed] [Google Scholar]
144. Oguri A, Suda M, Totsuka Y, Sugimura T, Wakabayashi K. Inhibitory effects of antioxidants on formation of heterocyclic amines. Mutat Res 1998; 402: 237–45. [DOI] [PubMed] [Google Scholar]
145. Armitage P, Doll R. The age distribution of cancer and a multistage theory of carcinogenesis. Br J Cancer 1954; 8: 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]
146. Sugimura T. Studies on environmental chemical carcinogenesis in Japan. Science 1986; 233: 312–8. [DOI] [PubMed] [Google Scholar]
147. Sugimura T, Nagao M, Wakabayashi K. How we should deal with unavoidable exposure of man to environmental mutagens: cooked food mutagen discovery, facts and lessons for cancer prevention. Mutat Res 2000; 447: 15–25. [DOI] [PubMed] [Google Scholar]
148. IARC . Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans 1992; 56: 169–242. [Google Scholar]
149. Ikeda M, Yoshimoto K, Yoshimura T, Kono S, Kato H, Kuratsune M. A cohort study on the possible association between broiled fish intake and cancer. Gann 1983; 74: 640–8. [PubMed] [Google Scholar]
150. Butler LM, Sinha R, Millikan RC, Martin CF, Newman B, Gammon MD, Ammerman AS, Sandler RS. Heterocyclic amines, meat intake, and association with colon cancer in a population‐based study. Am J Epidemiol 2003; 157: 434–45. [DOI] [PubMed] [Google Scholar]
151. Le Marchand L, Donlon T, Seifried A, Wilkens LR. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11: 1019–24. [PubMed] [Google Scholar]
152. Augustsson K, Skog K, Jagerstad M, Dickman PW, Steineck G. Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population‐based study. Lancet 1999; 353: 703–7. [DOI] [PubMed] [Google Scholar]
153. Roberts L. In: Thomas L, editor. Cancer today: Origins, prevention, and treatment. Washington : Institute of Medicine/National Academy Press; 1984. p. 68–9. [Google Scholar]
154. The National Food Administration, Sweden . Acrylamide in heat‐processed foods. Report of The National Food Administration. 2002-06-06. (http://www.slv.se/engdefault.asp?FrameLocation=/templatesSLV/SLV_DocumentList____4089.asp)
155. IARC . Some industrial chemicals‐acrylamide. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 1994; 60: 389–433. [PMC free article] [PubMed] [Google Scholar]
156. Hagmar L, Tornqvist M, Nordander C, Rosen I, Bruze F, Kautianinen A, Magnusson A‐L, Malmberg B, Aprea P, Ranath F, Axmon A. Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose. Scand J Work Environ Health 2001; 27: 219–26. [DOI] [PubMed] [Google Scholar]
157. Widmark EMP. Presence of cancer‐producing substances in roasted food. Nature 1939; 143: 984. [Google Scholar]

[b1] 1. Furth J, Lorenz E. Carcinogenesis by ionizing radiations. In: Hollaender A, editor. Radiation Biology. vol 1. New York : McGraw‐Hill; 1954. p. 1145. [Google Scholar]

[b2] 2. Pott P. Chirurgical observations relative to the cataract, the polyps of the nose, the cancer of the scrotum, the different kinds of ruptures, and the mortification of the toes and feet. London : Hawes, Clarke and Collins; 1775. [Google Scholar]

[b3] 3. Rehn L. Biasengeschwülste bei Fuchsin‐Arbeitern. Arch Klin Chir 1895; 50: 588–600. [Google Scholar]

[b4] 4. Härting GH, Hesse W. Der Lungenkrebs, die Bergkrankheit in den Schneeberger Gruben. Vrtijschr gerlichtl Med 1879; 30: 296–309and 31: 102–32. [Google Scholar]

[b5] 5. Spirtas R, Kaminski R. Angiosarcoma of the liver in vinyl chloride/polyvinyl chloride workers. Update of the NIOSH Register. J Occup Med 1977; 20: 427–9. [PubMed] [Google Scholar]

[b6] 6. Friend SH, Bernards R, Rogeij S, Weinberg RA, Rapaport JM, Albert DM, Dryja TP. A human DNA segment with properties of the gene that predisposes to retinoblastoma and osteosarcoma. Nature 1986; 323: 643–6. [DOI] [PubMed] [Google Scholar]

[b7] 7. Nishisho I, Nakamura Y, Miyoshi Y, Miki Y, Ando H, Horii A, Koyama K, Utsunomiya J, Baba S, Hedge P. Mutations of chromosome 5q21 genes in FAP and colorectal cancer patients. Science 1991; 253: 665–9. [DOI] [PubMed] [Google Scholar]

[b8] 8. Miki Y, Swensen J, Shattuck‐Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W et al. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 1994; 266: 66–71. [DOI] [PubMed] [Google Scholar]

[b9] 9. Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory S, Gumbs C, Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature 1995; 378: 762–3. [DOI] [PubMed] [Google Scholar]

[b10] 10. Guilford P, Hopkins J, Harraway J, McLeod M, McLeod N, Harawira P, Taite H, Scoular R, Miller A, Reeve AE. E‐Cadherin germline mutations in familial gastric cancer. Nature 1998; 26: 402–5. [DOI] [PubMed] [Google Scholar]

[b11] 11. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer—analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med 2000; 343: 78–85. [DOI] [PubMed] [Google Scholar]

[b12] 12. Doll R, Peto R. The causes of cancer: quantitative estimates of avoidable risks of cancer in the United States today. J Natl Cancer Inst 1981; 66: 1191–308. [PubMed] [Google Scholar]

[b13] 13. Parkin DM. Global cancer statistics in the year 2000. Lancet Oncol 2001; 2: 533–43. [DOI] [PubMed] [Google Scholar]

[b14] 14. McCann J, Ames BN. Detection of carcinogens as mutagens in the Salmonella/microsome test: assay of 300 chemicals: discussion. Proc Natl Acad Sci USA 1976; 73: 950–4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b15] 15. Sugimura T, Sato S, Nagao M, Yahagi T, Matsushima T, Seino Y, Takeuchi M, Kawachi T. Overlapping of carcinogens and mutagens. In: Magee PN, Takayama S, Sugimura T, Matushima T, editors. Fundamentals in cancer prevention. Tokyo : Univ Tokyo Press/Baltimore: Univ Park Press; 1976. p. 191–215. [Google Scholar]

[b16] 16. Nagao M, Sugimura T, Matsushima T. Environmental mutagens and carcinogens. Annu Rev Genet 1978; 12: 117–59. [DOI] [PubMed] [Google Scholar]

[b17] 17. Zeiger E, Anderson B, Haworth S, Lawlor T, Mortelmans K. Salmonella mutagenicity tests. V. Results from the testing of 311 chemicals. Environ Mol Mutagen 1992; 19 Suppl 21: 2–141. [DOI] [PubMed] [Google Scholar]

[b18] 18. IARC monographs on the evaluation of carcinogenic risks to humans. Overall evaluations of carcinogenicity: An updating of IARC monographs volumes 1 to 42. IARC monographs supplement 7. Lyon : IARC; 1987. p. 83–7. [PubMed] [Google Scholar]

[b19] 19. van Egmond HP, Dekker WH. Worldwide regulations for mycotoxins and phycotoxins in Rome, Italy. 1996 (May 2731). The 9th IUPAC International Symposium on Mycotoxins and Phycotoxins.

[b20] 20. Laqueur GL. Carcinogenic effects of cycad meal and cycasin, methyl‐azoxymethanol glycoside, in rats and effects of cycasin in germ free rats. Fed Proc 1964; 23: 1386–8. [PubMed] [Google Scholar]

[b21] 21. Evans IA, Mason J. Carcinogenic activity of bracken. Nature 1965; 208: 913–4. [DOI] [PubMed] [Google Scholar]

[b22] 22. van der Hoven JC, Aquilide A. A new mutagenic compound isolated from bracken fern (Pteridium aquilinum (L.) Kuhn). Carcinogenesis 1983; 4: 1587–90. [DOI] [PubMed] [Google Scholar]

[b23] 23. Kondo S, Ichikawa‐Ryo H. Testing and classification of mutagenicity of furylfuramide in Escherichi coli. Jpn J Genet 1973; 48: 295–300. [Google Scholar]

[b24] 24. Kada T. Escherichia coli mutagenicity of furylfuramide, Jpn J Genet 1973; 48: 301–5. [Google Scholar]

[b25] 25. Yahagi T, Matsushima T, Nagao M, Seino Y, Sugimura T, Bryan GT. Mutagenicity of nitrofuran derivatives on a bacterial tester strain with an R factor plasmid. Mutat Res 1976; 40: 9–14. [DOI] [PubMed] [Google Scholar]

[b26] 26. Ikeda Y, Horiuchi S, Furuya T, Uchida O, Suzuki K, Azegami J. Induction of gastric tumors in mice by feeding of furylfuramide. Food Sanitation Study Council 1974; Ministry of Health and Welfare, Japan . [Google Scholar]

[b27] 27. Sano T, Kawachi T, Matsukura N, Sasajima K, Sugimura T. Carcinogenicity of food additive, AF‐2, in hamsters and mice. Z Krebsforsch 1977; 89: 61–8. [DOI] [PubMed] [Google Scholar]

[b28] 28. Sugimura T, Nagao M, Kawachi T, Honda M, Yahagi T, Seino Y, Sato S, Matsukura N, Matsushima T, Shirai A, Sawamura M, Matsumoto H. Mutagen‐car‐cinogens in foods with special reference to highly mutagenic pyrolytic products in broiled foods. In: Hiatt HH, Watson JD, Winsten JA, editors. Origins of human cancer. New York : Cold Spring Harbor; 1977. p. 1561–77. [Google Scholar]

[b29] 29. Nagao M, Honda M, Seino Y, Yahagi T, Sugimura T. Mutagenicities of smoke condensates and the charred surface of fish and meat. Cancer Lett 1977; 2: 221–6. [DOI] [PubMed] [Google Scholar]

[b30] 30. Commoner B, Vithayathil AJ, Dolora P, Nair S, Madyastha P, Cuca GC. Formation of mutagens in beef and beef extract during cooking. Science 1978; 201: 913–6. [DOI] [PubMed] [Google Scholar]

[b31] 31. Sugimura T, Kawachi T, Nagao M, Yahagi T, Seino Y, Okamoto T, Shudo K, Kosuge T, Wakabayashi K, Iitaka T, Itai A. Mutagenic principle(s) in tryptophan and phenylalanine pyrolysis products. Proc Jpn Acad 1977; 53: 58–61. [Google Scholar]

[b32] 32. Yamamoto T, Tsuji K, Kosuge T, Okamoto T, Shudo K, Takeda K, Iitaka K, Yamaguchi K, Seino Y, Yahagi T, Nagao M, Sugimura T. Isolation and structure determination of mutagenic substances in L‐glutamic acid pyrolysate. Proc Jpn Acad 1978; 54B: 248–50. [Google Scholar]

[b33] 33. Yoshida D, Matsumoto T, Yoshimura R, Matsuzaki T. Mutagencity of amino‐α‐carboline in pyrolysis products of soybean globulin. Biochem Biophys Res Commun 1978; 83: 915–20. [DOI] [PubMed] [Google Scholar]

[b34] 34. Spingarn NE, Kasai H, Vuolo LL, Nishimura S, Yamaizumi Z, Sugimura T, Matsushima T, Weisburger JH. Formation of mutagens in cooked foods. III. Isolation of potent mutagens from beef. Cancer Lett 1980; 9: 177–83. [DOI] [PubMed] [Google Scholar]

[b35] 35. Wakabayashi K, Nagao M, Esumi H, Sugimura T. Food‐derived mutagens and carcinogens. Cancer Res 1992; 52 Suppl: 2092s–8s. [PubMed] [Google Scholar]

[b36] 36. Kasai H, Yamaizumi Z, Wakabayashi K, Nagao M, Sugimura T, Tokoyama S, Miyazawa T, Spingrn NE, Weisburger JH, Nishimura S. Potent novel mutagens produced by broiling fish under normal conditions. Proc Jpn Acad 1980; 56B: 278–83. [Google Scholar]

[b37] 37. Kasai H, Yamaizumi Z, Wakabayashi K, Nagao M, Sugimura T, Yokoyama S, Miyazawa T, Nishimura T. Structure and chemical synthesis of MeIQ, a potent mutagen isolated from broiled fish. Chem Lett 1980; 1391–4. [Google Scholar]

[b38] 38. Kasai H, Yamaizumi Z, Shiomi T, Yokoyama S, Miyazawa T, Wakabayashi K, Nagao M, Sugimura T, Nishimura S. Structure of a potent mutagen isolated from fried beef. Chem Lett 1981; 485–8. [Google Scholar]

[b39] 39. Felton JS, Knize MG, Shen NH, Lewis PR, Andresen BD, Happe J, Hatch FT. The isolation and identification of a new mutagen from fried ground beef: 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) Carcinogenesis 1986; 7: 1081–6. [DOI] [PubMed] [Google Scholar]

[b40] 40. Tsuda M, Negishi C, Makino R, Sato S, Yamaizumi Z, Hirayama T, Sugimura T. Use of nitrite and hypochlorite treatments in determination of the contributions of IQ‐type and non‐IQ‐type heterocyclic amines to the mutagenicities in crude pyrolyzed materials, Mutat Res 1985; 147: 335–41. [DOI] [PubMed] [Google Scholar]

[b41] 41. Jägerstad M, Lase Reutersward A, Olsson R, Grivas S, Nyhammar T, Olsson K, Dahlqvist A. Creatin(in)e and Maillard reaction products as precursors of mutagenic compounds: effects of various amino acids. Food Chem 1983; 12: 239–44. [Google Scholar]

[b42] 42. Felton JS, Jägerstad M, Knize MG, Skog K, Wakabayashi K. Contents in foods, beverages and tobacco. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 31–71. [Google Scholar]

[b43] 43. Nagao M. Mutagenicity. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 163–95. [Google Scholar]

[b44] 44. Terada M, Nagao M, Nakayasu M, Sakamoto H, Nakasato F, Sugimura T. Mutagenic activities of herterocyclic amines in Chinese hamster lung cells in culture. Environ Health Perspect 1986; 67: 117–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b45] 45. Thompson LH, Tucker JD, Stewart SA, Christense ML, Salazar EP, Carrano AV, Felton JS. Genotoxicity of compounds from cooked beef in repair‐deficient CHO cells versus Salmonella mutagenicity. Mutagenesis 1987; 2: 483–7. [DOI] [PubMed] [Google Scholar]

[b46] 46. Nagao M. A new approach to risk estimation of food‐borne carcinogens‐heterocyclic amines‐based on molecular information. Mutat Res 1999; 431: 3–12. [DOI] [PubMed] [Google Scholar]

[b47] 47. Okochi E, Watanabe N, Shimada Y, Takahashi S, Wakazono K, Shirai T, Sugimura T, Nagao M, Ushijima T. Preferential induction of guanine deletion at 5′‐GGGA‐3′ in rat mammary glands by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Carcinogenesis 1999; 20: 1933–8. [DOI] [PubMed] [Google Scholar]

[b48] 48. Okonogi H, Ushijima T, Zhang XB, Heddle JA, Suzuki T, Sofuni T, Felton JS, Ticker JD, Sugimura T, Nagao M. Agreement of mutational characteristics of heterocyclic amines in lacI of the Big Blue^® mouse with those in tumor related genes in rodents. Carcinogenesis 1997; 18: 745–8. [DOI] [PubMed] [Google Scholar]

[b49] 49. Nagao M, Ushijma T, Toyota M, Inoue R, Sugimura T. Genetic changes induced by heterocyclic amines. Mutat Res 1997; 376: 161–7. [DOI] [PubMed] [Google Scholar]

[b50] 50. Burnouf DY, Miturski R, Nagao M, Nakagama H, Nothisen M, Wagner J, Fuchs RPP. Early detection of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced mutations within the Apc gene of rat colon. Carcinogenesis 2001; 22: 329–35. [DOI] [PubMed] [Google Scholar]

[b51] 51. Nagao M. A new approach to risk estimation of food‐borne carcinogens—heterocyclic amines—based on molecular information. Mutat Res 1999; 431: 3–12. [DOI] [PubMed] [Google Scholar]

[b52] 52. Matsukura N, Kawachi T, Morino K, Ohgaki H, Sugimura T, Takayama S. Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolysate. Science 1981; 213: 346–7. [DOI] [PubMed] [Google Scholar]

[b53] 53. Ohgaki H, Matsukura N, Morino K, Kawachi T, Sugimura T, Takayama S. Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates. Carcinogenesis 1984; 5: 815–9. [DOI] [PubMed] [Google Scholar]

[b54] 54. Ohgaki H, Kusama K, Matsukura N, Morino K, Hasegawa H, Sato S, Takayama S, Sugimura T. Carcinogenicity in mice of a mutagenic compound, 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, from broiled sardine, cooked beef and beef extract. Carcinogenesis 1984; 5: 921–4. [DOI] [PubMed] [Google Scholar]

[b55] 55. Ohgaki H, Hasegawa H, Suenaga M, Sato S, Takayama S, Sugimura T. Induction of hepatocellular carcinoma and highly metastatic squamous cell carcinomas in the forestomach of mice by feeding 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoline. Carcinogenesis 1986; 7: 1889–93. [DOI] [PubMed] [Google Scholar]

[b56] 56. Ohgaki H, Hasegawa H, Suenaga M, Sato S, Takayama S, Sugimura T. Carcinogenicity in mice of a mutagenic compound, 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx) from cooked foods. Carcinogenesis 1987; 8: 665–8. [DOI] [PubMed] [Google Scholar]

[b57] 57. Fujita H, Nagano K, Ochiai M, Ushijima T, Sugimura T, Nagao M, Matsushima T. Difference in target organs in carcinogenesis with a heterocyclic amine, 2‐amino‐3,4‐dimethylimido[4,5‐f]quinoline, in different strains of mice. Jpn J Cancer Res 1999; 90: 1203–6. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b58] 58. Esumi H, Ohgaki H, Kohzen E, Takayama S, Sugimura T. Induction of lymphoma in CDF1 mice by the food mutagen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Jpn J Cancer Res 1989; 80: 1176–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b59] 59. Takayama S, Nakatsuru Y, Ohagaki H, Sato S, Sugimura T. Carcinogenicity in rats of a mutagenic compound, 3‐amino‐1,4‐dimethyl‐5H‐pyrido[4,3‐b]indole from tryptophan pyrolsate. Jpn J Cancer Res 1985; 76: 815–7. [PubMed] [Google Scholar]

[b60] 60. Takahashi M, Toyoda K, Aze Y, Furuta K, Mitsumori K, Hayashi Y. The rat urinary bladder as a new target of heterocyclic amine carcinogenicity: tumor induc‐tionby 3‐amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole acetate. Jpn J cancer Res 1993; 84: 852–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b61] 61. Takayama S, Masuda M, Mogami M, Ohgaki H, Sato S, Sugimura T. Induction of cancers in the intestine, liver and various other organs of rats by feeding mutagens from glutamic acid pyrolysate. Gann 1984; 75: 207–13. [PubMed] [Google Scholar]

[b62] 62. Tamano S, Hasegawa R, Hagiwara A, Nagao M, Sugimura T, Ito N. Carcinogenicity of a mutagenic compound from food, 2‐amino‐3‐methyl‐9H‐pyrido[2,3‐b]indole (MeAαC), in male F344 rats. Carcinogenesis 1994; 15: 2009–15. [DOI] [PubMed] [Google Scholar]

[b63] 63. Takayama S, Nakatsuru Y, Masuda M, Ohgaki H, Sato S, Sugimura T. Demonstration of carcinogenicity in F344 rats of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline from broiled sardine, fried beef and beef extract. Gann 1984; 75: 467–70. [PubMed] [Google Scholar]

[b64] 64. Kato T, Migita H, Ohgaki H, Sato S, Takayama S, Sugimura T. Induction of tumors in the Zymbal gland, oral cavity, colon, skin and mammary gland of F344 rats by a mutagenic compound, 2‐amino‐3,4‐dimethylimidazo[4,5‐f]quinoline. Carcinogenesis 1989; 10: 601–3. [DOI] [PubMed] [Google Scholar]

[b65] 65. Kato T, Ohgaki H, Hasegawa H, Sato S, Takayama S, Sugimura T. Carcinogenicity in rats of a mutagenic compound, 2‐amino‐3,8‐dimethylimi‐dazo[4,5‐f]quinoxaline. Carcinogenesis 1988; 9: 71–3. [DOI] [PubMed] [Google Scholar]

[b66] 66. Ito N, Hasegawa R, Sano M, Tamano S, Esumi H, Takayama S, Sugimura T. A new colon and mammary carcinogen in cooked food, 2‐amino‐1‐methyl‐6‐phe‐nylimidazo[4,5‐b]pyridine (PhIP). Carcinogenesis 1991; 12: 1503–6. [DOI] [PubMed] [Google Scholar]

[b67] 67. Shirai T, Sano M, Tamano S, Takahashi S, Hirose M, Futakuchi M, Hasegawa R, Imaida K, Matsumoto K, Wakabayashi K, Sugimura T, Ito N. The prostate: a target for carcinogenicity of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) derived from cooked foods. Cancer Res 1997; 57: 195–8. [PubMed] [Google Scholar]

[b68] 68. Ochiai M, Imai H, Sugimura T, Nagao M, Nakagama H. Induction of intestinal tumors and lymphomas in C57BL/6N mice by a food‐borne carcinogen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Jpn J Cancer Res 2002; 93: 478–83. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b69] 69. Takayama S, Nakatsuru Y, Ohgaki H, Sato S, Sugimura T. Atrophy of salivary glands and pancreas of rats fed on diet with amino‐methyl‐α‐carboline. Proc Jpn Acad 1985; 61 Ser B: 277–80. [Google Scholar]

[b70] 70. Tanaka T, Barnes WS, Williams GM, Weisburger JH. Multipotential carcinogenicity of the fried food mutagen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline in rats. Gann 1985; 76: 570–6. [PubMed] [Google Scholar]

[b71] 71. Adamson RH, Thorgeirsson UP, Snyderwine EG, Thorgeirsson SS, Reeves J, Dalgard DW, Takayama S, Sugimura T. Carcinogenicity of 2‐amino‐3‐methylimi‐dazo[4,5‐f]quinoline in nonhuman primates: induction of tumors in three macaques. Jpn J Cancer Res 1990; 81: 10–4. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b72] 72. Yamazoe Y, Shimada M, Kamataki T, Kato R. Microsomal activation of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, a pyrolysate of sardine and beef extracts, to a mutagenic intermediate. Cancer Res 1983; 43: 5768–74. [PubMed] [Google Scholar]

[b73] 73. Shimada T, Guengerich FP. Activation of amino‐α‐carboline, 2‐amino‐1‐methyl‐6‐phenyimidazo[4,5‐b]pyridine, and a copper phthalocyanine cellulose extract of cigarette smoke condensate by cytochrome P‐450 enzymes in rat and human liver microsomes. Cancer Res 1991; 56: 2979–84. [PubMed] [Google Scholar]

[b74] 74. Hammons GJ, Miton D, Stepps K, Guengerrich FP, Tukey RH, Kadlubar FF. Metabolism of carcinogenic heterocyclic and aromatic amines by recombinant human cytochrome P450 enzymes. Carcinogenesis 1997; 18: 851–4. [DOI] [PubMed] [Google Scholar]

[b75] 75. Turesky R, Constable A, Fay LB, Guengerich FP. Interspecies differences in metabolism of heterocyclic amines by rat and human P450 1A2. Cancer Lett 1999; 143: 109–12. [DOI] [PubMed] [Google Scholar]

[b76] 76. Hickman D, Pope J, Patil S, Fakis G, Smelt V, Stanley L, Payton M, Unadkat J, Sim E. Expression of arylamine N‐acetyltransferase in human intestine. Gut 1998; 42: 402–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b77] 77. Hein DW, Doll MA, Rustan TD, Gray K, Feng Y, Ferguson RJ, Grant DM. Metabolic activation and deactivation of arylamine carcinogens by recombinant human NAT1 and polymorphic NAT2 acetyltransferases. Carcinogenesis 1993; 14: 1633–8. [DOI] [PubMed] [Google Scholar]

[b78] 78. Minchin RF, Reeves PT, Teitel CH, McManus ME, Mojarrabi B, Illett KF, Kadlubar FF. N‐and O‐acetylation of aromatic and HCA carcinogens by human monomorphic and polymorphic acetyltransferases expressed in COS‐1 cells. Biochem Biophys Res Commun 1992; 185: 839–44. [DOI] [PubMed] [Google Scholar]

[b79] 79. LeMarchand L, Hankin JH, Pierce LM, Sinha R, Nerurkar PV, Franke AA, Wilkens LR, Kolonel LN, Donlon T, Seifried A, Custer LJ, Lum‐Jones A, Chang W. Well‐done red meat, metabolic phenotypes and colorectal cancer in Hawaii. Mutat Res 2002; 506–507: 205–214. [DOI] [PubMed] [Google Scholar]

[b80] 80. Ishibe N, Sinha R, Hein DW, Kulldorff M, Strickland P, Fretland AJ, Chow WH, Kadlubar FF, Lang NP, Rothman N. Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas. Pharmacogenetics 2002; 12: 145–50. [DOI] [PubMed] [Google Scholar]

[b81] 81. Snyderwine EG, Roller PP, Adamson RH, Sato S, Thorgeirsson SS. Reaction of N‐hydroxylamine and N‐acetoxy derivatives of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline with DNA. Synthesis and identification of N‐(deoxyguanosin‐8‐yl)‐IQ. Carcinogenesis 1988; 9: 1061–5. [DOI] [PubMed] [Google Scholar]

[b82] 82. Nagaoka H, Wakabayashi K, Kim S‐B, Kim I‐S, Tanaka Y, Ochiai M, Tada A, Nukaya H, Sugimura T, Nagao M. Adduct formation at C‐8 of guanine on in vitro reaction of the ultimate form of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine with 2′‐deoxyguanosine and its phosphate esters. Jpn J Cancer Res 1992; 83: 1025–9. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b83] 83. Turesky RJ, Rossi SC, Welti D, Lay JO Jr, Kadlubar FF. Characterization of DNA adducts formed in vitro by reaction of N‐hydroxy‐2‐amino‐3‐methylimidazo[4,5‐f]quinoline and N‐hydroxy‐2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline at C‐8 and N² atoms of guanine. Chem Res Toxicol 1992; 5: 479–90. [DOI] [PubMed] [Google Scholar]

[b84] 84. Brown K, Hingerty BE, Guenther EA, Krishnan VV, Broyde S, Turteltaub KW, Cosman M. Solution structure of the 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b] pyridine C8‐deoxyguanosine adduct in duplex DNA. Proc Natl Acad Sci USA 2001; 98: 8507–12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b85] 85. Tatemachi M, Nomura S, Ogura T, Sone H, Nagata H, Esumi H. Mutagenic activation of environmental carcinogens by microsomes of gastric mucosa with intestinal metaplasia. Cancer Res 1999; 15: 3893–8. [PubMed] [Google Scholar]

[b86] 86. Guy PA, Gremaud E, Richoz J, Turesky RJ. Quantitative analysis of mutagenic heterocyclic aromatic amines in cooked meat using liquid chromatography‐atmospheric pressure chemical ionization tandem mass spectrometry. J Chromatogr A 2000; 883: 89–102. [DOI] [PubMed] [Google Scholar]

[b87] 87. Kataoka H, Kajima KK. Analysis of heterocyclic amines as their N‐dimethylami‐nomethylene derivatives by gas chromatography with nitrogen‐phophorus selective detection. J Chromatogr A 1997; 767: 187–94. [Google Scholar]

[b88] 88. Kataoka H, Nishioka S, Kobayashi M, Hanaoka T, Tsugane S. Analysis of mutagenic heterocyclic amines in cooked food samples by gas chromatography with nitrogen‐phosphorus detector. Bull Environ Contam Toxicol 2002; 69: 682–9. [DOI] [PubMed] [Google Scholar]

[b89] 89. Felton JS, Knize MG, Salmon CP, Malfatti MA, Kulp KS. Human exposure to heterocyclic amine food mutagens/carcinogens: relevance to breast cancer. Environ Mol Mutagen 2002; 39: 112–8. [DOI] [PubMed] [Google Scholar]

[b90] 90. Knize MG, Salmon CP, Felton JS. Mutagenic activity and heterocyclic amine carcinogens in commercial pet foods. Mutat Res 2003; 539: 195–201. [DOI] [PubMed] [Google Scholar]

[b91] 91. Ushiyama H, Wakabayashi K, Hirose M, Ito H, Sugimura T, Nagao M. Presence of carcinogenic heterocyclic amines in urine of healthy volunteers eating normal diet, but not of inpatients receiving parenteral alimentation. Carcinogenesis 1991; 12: 1417–22. [DOI] [PubMed] [Google Scholar]

[b92] 92. DeBruin LS, Martos PA, Josephy PD. Detection of PhIP (2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine) in the milk of healthy women. Chem Res Toxicol 2001; 14: 1523–8. [DOI] [PubMed] [Google Scholar]

[b93] 93. Gorlewska‐Roberts K, Green B, Fares M, Ambrosone CB, Kadlbar FF. Carcinogen‐DNA adducts in human breast epithelial cells. Environ Mol Mutagen 2002; 39: 184–92. [DOI] [PubMed] [Google Scholar]

[b94] 94. Takayama K, Yamashita K, Wakabayashi K, Sugimura T, Nagao M. DNA modification by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine in rats. Jpn J Cancer Res 1989; 80: 1145–8. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b95] 95. Skipper PL, Tannenbaum SR. Protein adducts in the molecular dosimetry of chemical carcinogens. Carcinogenesis 1990; 11: 507–18. [DOI] [PubMed] [Google Scholar]

[b96] 96. Umemoto A, Monden Y, Tsuda M, Grivas S, Sugimura T. Oxidation of the 2‐hydroxyamino derivative of 2‐amino‐6‐methyldipyrido[1,2‐a:3′,2′‐d]imidazole (Glu‐P‐1) to its 2‐nitroso form, an ultimate form reacting with hemoglobin thiol groups. Biochem Biophys Res Commun 1988; 151: 1326–31. [DOI] [PubMed] [Google Scholar]

[b97] 97. Magagnotti C, Orsi F, Bagnati R, Celli N, Rotilio D, Fanelli R, Airoldi L. Effect of diet on serum albumin and hemoglobin adducts of 2‐amino‐1‐methyl‐6‐phenylim‐idazo[4,5‐b]pyridine (PhIP) in humans. Int J Cancer 2000; 88: 1–6. [DOI] [PubMed] [Google Scholar]

[b98] 98. Nagao M, Yahagi T, Honda M, Seino Y, Matsushima T, Sugimura T. Demonstration of mutagenicity of aniline and o‐toluidine by norharman. Proc Jpn Acad 1977: 53: 34–7. [Google Scholar]

[b99] 99. Totsuka Y, Hada N, Matsumoto K, Kawahara N, Murakami Y, Yokoyama Y, Sugimura T, Wakabayashi K. Structure determination of a mutagenic aminophenylnorharman produced by the co‐mutagen norharman with aniline. Carcinogenesis 1998; 19: 1995–2000. [DOI] [PubMed] [Google Scholar]

[b100] 100. Totsuka Y, Kataoka H, Takamura‐Enya T, Kawahara N, Nishigaki R, Sugimura T, Wakabayashi K. Structure of DNA adduct formed with aminophenylnorharman, being responsible for the comutagenic action of norharman with aniline. Chem Res Toxicol 2002; 15: 1288–94. [DOI] [PubMed] [Google Scholar]

[b101] 101. Totsuka Y, Kataoka H, Takamura‐Enya T, Sugimura T, Wakabayashi K. In vitro and in vivo formation of aminophenylnorharman from norharman and aniline. Mutat Res 2002; 506–507: 49–54. [DOI] [PubMed] [Google Scholar]

[b102] 102. Sugimura T. A new concept of co‐mutagenicity from a phenomenon forgotten for the past two decades: is it more important than previously expected?; Environ Health Perspect 1998; 106: A522–3. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b103] 103. Sugimura T, Nagao M, Wakabayashi K. Complex factors pertinent to human hazard risk. In: Nagao M, Sugimura T, editors. Food borne carcinogens: Heterocyclic amines. Chichester : John Wiley & Sons Ltd; 2000. p. 349–59. [Google Scholar]

[b104] 104. Rohrmann S, Becker N. Development of a short questionnaire to assess the dietary intake of heterocyclic aromatic amines. Public Health Nutr 2002; 5: 699–705. [DOI] [PubMed] [Google Scholar]

[b105] 105. Nowell S, Coles B, Sinha R, Macleod S, Ratnasinghe DL, Stotts C, Kadlubar FF, Ambrosone CB, Lang NP. Analysis of total meat intake and exposure to individual heterocyclic amines in a case‐control study of colorectal cancer: contribution of metabolic variation to risk. Mutat Res 2002; 506–507: 175–85. [DOI] [PubMed] [Google Scholar]

[b106] 106. Kobayashi M, Hanaoka T, Nishioka S, Kataoka H, Tsugane S. Estimation of dietary HCA intakes in a large‐scale population‐based prospective study in Japan. Mutat Res 2002; 506–507: 233–41. [DOI] [PubMed] [Google Scholar]

[b107] 107. Hasegawa R, Tanaka H, Tamano S, Shirai T, Nagao M, Sugimura T, Ito N. Synergistic enhancement of small and large intestinal carcinogenesis by combined treatment of rats with five heterocyclic amines in a medium‐term multi‐organ bio‐assay. Carcinogenesis 1994; 15: 2567–73. [DOI] [PubMed] [Google Scholar]

[b108] 108. Takahashi M, Furukawa F, Miyakawa Y, Sato H, Hasegawa R, Hayashi Y. 3‐Amino‐1‐methyl‐5H‐pyrido[4,3‐b]indole initiates two‐stage carcinogenesis in mouse skin but is not a complete carcinogen. Jpn J Cancer Res 1986; 77: 509–13. [PubMed] [Google Scholar]

[b109] 109. Nagao M, Ushijima T, Toyota M, Inoue R, Sugimura T. Genetic changes induced by heterocyclic amines. Mutat Res 1997; 376: 161–7. [DOI] [PubMed] [Google Scholar]

[b110] 110. Dashwood RH, Suzui M, Nakagama H, Sugimura T, Nagao M. High frequency of β‐catenin (Ctnnb1) mutations in the colon tumors induced by two heterocyclic amines in the F344 rat. Cancer Res 1998; 58: 1127–9. [PubMed] [Google Scholar]

[b111] 111. Yu M, Snyderwine EG. H‐ras oncogene mutations during development of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced rat mammary gland cancer. Carcinogenesis 2002; 23: 2123–8. [DOI] [PubMed] [Google Scholar]

[b112] 112. Qiu C, Shan L, Yu M, Snyderwine EG. Deregulation of the cyclin D1/Cdk4 retin‐oblastoma pathway in rat mammary gland carcinomas induced by the food‐derived carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine. Cancer Res 2003; 63: 5674–8. [PubMed] [Google Scholar]

[b113] 113. Watanabe N, Okochi E, Hirayama Y, Shimada Y, Yanagihara K, Yoshida MC, Takahashi S, Mochizuki M, Sugimura T, Nagao M, Ushijima T. Single nucleotide instability without microsatellite instability in rat mammary carcinomas. Cancer Res 2001; 61: 2632–40. [PubMed] [Google Scholar]

[b114] 114. Okochi E, Watanabe N, Sugimura T, Ushijima T. Single nucleotide instability: a wide involvement in human and rat mammary carcinogenesis? Single nucleotide instability without microsatellite instability in rat mammary carcinomas. Mutat Res 2002; 506–507: 101–11. [DOI] [PubMed] [Google Scholar]

[b115] 115. Ubagai T, Ochiai M, Kawamori T, Imai H, Sugimura T, Nagao M, Nakagama H. Efficient induction of rat large intestinal tumors with a new spectrum of mutations by intermittent administration of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyri‐dine in combination with a high fat diet. Carcinogenesis 2002; 23: 197–200. [DOI] [PubMed] [Google Scholar]

[b116] 116. Ghoshal A, Preisegger KH, Takayama S, Thorgeirsson SS, Snyderwine EG. Induction of mammary tumors in female Sprague‐Dawley rats by the food‐derived carcinogen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine and effect of dietary fat. Carcinogenesis 1994; 15: 2429–33. [DOI] [PubMed] [Google Scholar]

[b117] 117. Takahashi M, Totsuka Y, Masuda M, Fukuda K, Oguri A, Yazawa K, Sugimura T, Wakabayashi K. Reduction in formation of 2‐amino‐1‐methyl‐6‐phenylimi‐dazo[4,5‐b]pyridine (PhIP)‐induced aberrant crypt foci in the rat colon by docosa‐hexaenoic acid (DHA). Carcinogenesis 1997; 18: 1937–41. [DOI] [PubMed] [Google Scholar]

[b118] 118. Liew C, Schut HAJ, Chin SF, Pariza MW, Dashwood RH. Protection of conjugated linoleic acids against 2‐amino‐3‐methylimidazo[4,5‐f]quinoline‐induced colon carcinogenesis in the F344 rats: a study of inhibitory mechanisms. Carcinogenesis 1995; 16: 3037–43. [DOI] [PubMed] [Google Scholar]

[b119] 119. Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S. Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst 2003; 95: 906–13. [DOI] [PubMed] [Google Scholar]

[b120] 120. Ohta T, Nakatsugi S, Watanabe K, Kawamori T, Ishikawa F, Morotomi M, Sugie S, Toda T, Sugimura T, Wakabayashi K. Inhibitory effects of Bifidobacterium‐fermented soy milk on 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine‐induced rat mammary carcinogenesis, with a partial contribution of its component isoflavones. Carcinogenesis 2000; 21: 937–41. [DOI] [PubMed] [Google Scholar]

[b121] 121. Hirose M, Hasegawa R, Kimura J, Akagi K, Yoshida Y, Tanaka H, Miki T, Satoh T, Wakabayashi K, Ito N, Shirai T. Inhibitory effects of 1‐O‐hexyl‐2,3,5‐trimethyl‐hydroquinone (HTHQ), green tea catechins and other antioxidants on 2‐amino‐6‐methyldipyrido[1,2‐a;3′,2′‐d]imidazole (Glu‐P‐1)‐induced rat hepatocarcinogenesis and dose‐dependent inhibition by HTHQ of lesion induction by Glu‐P‐1 or 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx). Carcinogenesis 1995; 16: 3049–55. [DOI] [PubMed] [Google Scholar]

[b122] 122. Hirose M, Akagi K, Hasegawa R, Yaono M, Satoh T, Hara Y, Wakabayashi K, Ito N. Chemoprevention of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced mammary gland carcinogenesis by antioxidants in F344 female rats. Carcinogenesis 1995; 16: 217–21. [DOI] [PubMed] [Google Scholar]

[b123] 123. Guo D, Schut HAJ, Davis CD, Snyderwine EG, Bailey GS, Dashwood RH. Protection by chlorophyllin and indole‐3‐carbinol against 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP)‐induced DNA adducts and colonic aberrant crypts in the F344 rats. Carcinogenesis 1995; 16: 2931–7. [DOI] [PubMed] [Google Scholar]

[b124] 124. Xu M, Bailey AC, Hernaez JF, Taoka CR, Schut HAJ, Dashwood RH. Protection by green tea, black tea, and indole‐3‐carbinol against 2‐amino‐3‐methylimi‐dazo[4,5‐f]quinoline‐induced DNA adducts and colonic aberrant crypts in the F344 rat. Carcinogenesis 1996; 17: 1429–34. [DOI] [PubMed] [Google Scholar]

[b125] 125. Dashwood RH. Modulation of heterocyclic amine‐induced mutagenicity and carcinogenicity: an 'A‐to‐Z' guide to chemopreventive agents, promoters, and transgenic models. Mutat Res 2002; 11: 89–112. [DOI] [PubMed] [Google Scholar]

[b126] 126. Tsuda H, Sekine K, Uehara N, Takasuka N, Moore MA, Konno Y, Nakashita K, Degawa M. Heterocyclic amine mixture carcinogenesis and its enhancement by caffeine in F344 rats. Cancer Lett 1999; 143: 229–34. [DOI] [PubMed] [Google Scholar]

[b127] 127. Reddy BS, Rivenson A. Inhibitory effect of Bifidobacterium longum on colon, mammary, and liver carcinogenesis induced by 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, a food mutagen. Cancer Res 1993; 53: 3914–8. [PubMed] [Google Scholar]

[b128] 128. Guo D, Horio DT, Grove JS, Dashwood RH. Inhibition by chlorophyllin of 2‐amino‐3‐methylimidazo[4,5‐f]quinoline‐induced tumorigenesis in the male F344 rat. Cancer Lett 1995; 95: 161–5. [DOI] [PubMed] [Google Scholar]

[b129] 129. Hasegawa R, Hirose M, Kato T, Hagiwara A, Boonyaphiphat P, Nagao M, Ito N, Shirai T. Inhibitory effect of chlorophyllin on PhIP‐induced mammary carcinogenesis in female F344 rats. Carcinogenesis 1995; 16: 2243–6. [DOI] [PubMed] [Google Scholar]

[b130] 130. Ohgaki H, Kawachi T, Matsukura N, Morino K, Miyamoto M, Sugimura T. Genetic control of susceptibility of rats to gastric carcinoma. Cancer Res 1983; 43: 3663–7. [PubMed] [Google Scholar]

[b131] 131. Ushijima T, Yamamoto M, Suzui M, Kuramoto T, Yoshida Y, Nomoto T, Tatematsu M, Sugimura T, Nagao M. Chromosomal mapping of genes controlling development, histological grade, depth of invasion, and size of rat stomach carcinomas. Cancer Res 2000; 60: 1092–6. [PubMed] [Google Scholar]

[b132] 132. Demant P. Cancer susceptibility in the mouse: genetics, biology and implications for human cancer. Nat Rev 2003; 4: 721–34. [DOI] [PubMed] [Google Scholar]

[b133] 133. Ruivenkamp CAL, van Wezel T, Zanon C, Stassen APM, Vlek C, Csikos T, Klous AM, Tripodis N, Perrakis A, Boerrigter L, Groot PC, Lindeman J, Mooi SK, Meijjer GA, Scholten G, Dauwerse H, Paces V, van Zandwijk N, van Ommen GJB, van Demant P. Ptprj is a candidate for the mouse colon‐cancer susceptibility locus Scc1 and is frequently deleted in human cancers. Nat Genet 2002; 31: 295–300. [DOI] [PubMed] [Google Scholar]

[b134] 134. Dietrich WF, Lander ES, Smith JS, Moser AR, Gould KA, Luongo C, Borenstein N, Dove W. Genetic identification of Mom‐1, a major modifier locus affecting Min‐induced intestinal neoplasia in the mouse. Cell 1993; 75: 631–9. [DOI] [PubMed] [Google Scholar]

[b135] 135. MacPhee M, Chepenik KP, Liddell RA, Nelson KK, Siracusa LD, Buchberg AM. The secretory phospholipase A2 gene is a candidate for the Mom1 locus, a major modifier of ApcMin‐induced intestinal neoplasia. Cell 1995; 81: 957–66. [DOI] [PubMed] [Google Scholar]

[b136] 136. Ishiguro Y, Ochiai M, Sugimura T, Nagao M, Nakagama H. Strain differences of rats in the susceptibility to aberrant crypt foci formation by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine: no implication of Apc and Pla2g2a genetic polymorphisms in differential susceptibility. Carcinogenesis 1999; 20: 1063–8. [DOI] [PubMed] [Google Scholar]

[b137] 137. Nakagama H, Souda K, Ochiai M, Ishiguro Y, Sugimura T, Nagao M. Genetic analysis of the susceptibility in rats to aberrant crypt foci formation by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine, PhIP. Cancer Lett 1999; 143: 205–9. [DOI] [PubMed] [Google Scholar]

[b138] 138. Knize MG, Kulp KS, Salmon CP, Keating GA, Felton JS. Factors affecting human heterocyclic amine intake and the metabolism of PhIP. Mutat Res 2002; 506–507, 153–62. [DOI] [PubMed] [Google Scholar]

[b139] 139. Persson E, Sjoholm I, Skog K. Effect of high water‐holding capacity on the formation of heterocyclic amines in fried beefburgers. J Agric Food Chem 2003; 51: 4472–7. [DOI] [PubMed] [Google Scholar]

[b140] 140. Underwood A, Springen K, Davis A. Cancer & diet. Newsweek 1998; Nov 30: 42–8. [Google Scholar]

[b141] 141. Salmon CP, Kinze MG, Panteleakos FN, Wu RW, Nelson DO, Felton JS. Minimization of heterocyclic amines and thermal inactivation of Escherichia coli in fried ground beef. J Natl Cancer Inst 2000; 92: 1773–8. [DOI] [PubMed] [Google Scholar]

[b142] 142. O'Neil. Hamburger safety may be partly in the flip. The New York Times 2000; Dec 5. [Google Scholar]

[b143] 143. Johansson M, Jägerstad M. Influence of edible oils and fatty acids on the formation of heterocyclic amines in a model system. Food Chem 1996; 56: 69–75. [DOI] [PubMed] [Google Scholar]

[b144] 144. Oguri A, Suda M, Totsuka Y, Sugimura T, Wakabayashi K. Inhibitory effects of antioxidants on formation of heterocyclic amines. Mutat Res 1998; 402: 237–45. [DOI] [PubMed] [Google Scholar]

[b145] 145. Armitage P, Doll R. The age distribution of cancer and a multistage theory of carcinogenesis. Br J Cancer 1954; 8: 1–12. [DOI] [PMC free article] [PubMed] [Google Scholar]

[b146] 146. Sugimura T. Studies on environmental chemical carcinogenesis in Japan. Science 1986; 233: 312–8. [DOI] [PubMed] [Google Scholar]

[b147] 147. Sugimura T, Nagao M, Wakabayashi K. How we should deal with unavoidable exposure of man to environmental mutagens: cooked food mutagen discovery, facts and lessons for cancer prevention. Mutat Res 2000; 447: 15–25. [DOI] [PubMed] [Google Scholar]

[b148] 148. IARC . Some naturally occurring substances: food items and constituents, heterocyclic aromatic amines and mycotoxins. IARC Monograph on the Evaluation of Carcinogenic Risks to Humans 1992; 56: 169–242. [Google Scholar]

[b149] 149. Ikeda M, Yoshimoto K, Yoshimura T, Kono S, Kato H, Kuratsune M. A cohort study on the possible association between broiled fish intake and cancer. Gann 1983; 74: 640–8. [PubMed] [Google Scholar]

[b150] 150. Butler LM, Sinha R, Millikan RC, Martin CF, Newman B, Gammon MD, Ammerman AS, Sandler RS. Heterocyclic amines, meat intake, and association with colon cancer in a population‐based study. Am J Epidemiol 2003; 157: 434–45. [DOI] [PubMed] [Google Scholar]

[b151] 151. Le Marchand L, Donlon T, Seifried A, Wilkens LR. Red meat intake, CYP2E1 genetic polymorphisms, and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2002; 11: 1019–24. [PubMed] [Google Scholar]

[b152] 152. Augustsson K, Skog K, Jagerstad M, Dickman PW, Steineck G. Dietary heterocyclic amines and cancer of the colon, rectum, bladder, and kidney: a population‐based study. Lancet 1999; 353: 703–7. [DOI] [PubMed] [Google Scholar]

[b153] 153. Roberts L. In: Thomas L, editor. Cancer today: Origins, prevention, and treatment. Washington : Institute of Medicine/National Academy Press; 1984. p. 68–9. [Google Scholar]

[b154] 154. The National Food Administration, Sweden . Acrylamide in heat‐processed foods. Report of The National Food Administration. 2002-06-06. (http://www.slv.se/engdefault.asp?FrameLocation=/templatesSLV/SLV_DocumentList____4089.asp)

[b155] 155. IARC . Some industrial chemicals‐acrylamide. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans 1994; 60: 389–433. [PMC free article] [PubMed] [Google Scholar]

[b156] 156. Hagmar L, Tornqvist M, Nordander C, Rosen I, Bruze F, Kautianinen A, Magnusson A‐L, Malmberg B, Aprea P, Ranath F, Axmon A. Health effects of occupational exposure to acrylamide using hemoglobin adducts as biomarkers of internal dose. Scand J Work Environ Health 2001; 27: 219–26. [DOI] [PubMed] [Google Scholar]

[b157] 157. Widmark EMP. Presence of cancer‐producing substances in roasted food. Nature 1939; 143: 984. [Google Scholar]

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Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish

Takashi Sugimura

Keiji Wakabayashi

Hitoshi Nakagama

Minako Nagao

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Heterocyclic amines: Mutagens/carcinogens produced during cooking of meat and fish

Takashi Sugimura

Keiji Wakabayashi

Hitoshi Nakagama

Minako Nagao

Abstract

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