Abstract
Dietary administration of 0.1, 0.05, or 0.025% 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) for two weeks combined with partial hepatectomy at the end of the first week and followed by long‐term treatment with phenobarbital (PB) or 3′‐methyl‐4‐dimethylaminoazobenzene (3′‐MeDAB) from week 3 to week 86 resulted in dose‐dependent development of liver and thyroid neoplastic and preneoplastic lesions. Quantitation of glutathione S‐transferase placental form (GST‐P)‐positive hepatocellular focal populations revealed a significant correlation of IQ concentration with lesion area, with a yield approximately equal to that generated by a similar dose of 2‐acetylaminofluorene. The fact that IQ was less toxic therefore allowed greater yields of hepatocellular carcinomas to be induced. The development of thyroid tumors initiated by the IQ treatment was significantly enhanced by the administration of PB, whereas Zymbal gland tumors induced by IQ did not show any correlation with either PB or 3′‐Me‐DAB treatment.
Keywords: Pyrolysis products, Carcinogenicity, Liver, Thyroid, Dose dependency
Full Text
The Full Text of this article is available as a PDF (349.6 KB).
REFERENCES
- 1. ) Matsukura , N. , Kawachi , T. , Morino , K. , Ohgaki , H. and Sugimura , T.Carcinogenicity in mice of mutagenic compounds from a tryptophan pyrolysate . Science , 213 , 346 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Ishikawa , T. , Takayama , S. , Kitagawa , T. , Kawachi , T. , Kinebuchi , M. , Matsukura , N. , Uchida , E. and Sugimura , T.In vivo experiments on tryptophan pyrolysis products . In “ Naturally Occurring Carcinogens‐Mutagens and Modulators of Carcinogenesis ,” ed. Miller E. C. , Miller J. A. , Hirono I. , Sugimura T. and Takayama S. , pp. 159 – 167 ( 1981. ). Japan Scientific Societies Press, Tokyo/University Park Press; , Baltimore . [Google Scholar]
- 3. ) Hosaka , S. , Matsushima , T. , Hirono , I. and Sugimura , T.Carcinogenic activity of 3‐amino‐1‐methyl‐5H‐pyrido[4,3 ‐b]indole (Tr‐P‐2), a pyrolysis product of tryptophan . Cancer Lett. , 13 , 23 – 28 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Takayama , S. , Nakatsuru , Y. , Ohgaki , H. , Sato , S. and Sugimura , T.Carcinogenicity in rats of a mutagenic compound, 3‐amino‐1,4‐dimethyl‐5H‐pyrido[4,3‐b]indole, from tryptophan pyrolysate . Jpn. J. Cancer Res. (Gann) , 76 , 815 – 817 ( 1985. ). [PubMed] [Google Scholar]
- 5. ) Takayama , S. , Masuda , M. , Mogami , M. , Ohgaki , H. , Sato , S. and Sugimura , T.Induction of cancers in the intestine, liver and various other organs of rats by feeding mutagens from glutamic acid pyrolysate . Gann , 75 , 207 – 213 ( 1984. ). [PubMed] [Google Scholar]
- 6. ) Ohgaki , H. , Matsukura , N. , Morino , K. , Kawachi , T. , Sugimura , T. and Takayama , S.Carcinogenicity in mice of mutagenic compounds from glutamic acid and soybean globulin pyrolysates . Carcinogenesis , 5 , 815 – 819 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Takayama , S. , Nakatsuru , Y. , Masuda , M. , Ohgaki , H. , Sato , S. and 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 , 75 , 467 – 470 ( 1984. ). [PubMed] [Google Scholar]
- 8. ) Ohgaki , H. , Kusama , K. , Matsukura , N. , Morino , K. , Hasegawa , H. , Sato , S. , Takayama , S. and 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 , 5 , 921 – 924 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Ohgaki , H. , Hasegawa , H. , Suenaga , M. , Sato , S. , Takayama , S. and Sugimura , T.Carcinogenicity in mice of a mutagenic compound, 2‐amino‐3,8‐dimethylimidazo[4,5‐f‐quinoxaline (MelQx) from cooked foods . Carcinogenesis , 8 , 665 – 668 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 10. ) Kato , T. , Ohgaki , H. , Hasegawa , H. , Saito , S. , Takayama , S. and Sugimura , T.Carcinogenicity in rats of a mutagenic compound, 2‐amino‐3,8‐dimethylimidazo [4,5‐f] quinoxaline . Carcinogenesis , 9 , 71 – 73 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Sugimura , T. , Nagao , M. , Kawachi , T. , Honda , M. , Yahagi , T. , Seino , Y. , Sato , S. and Matsukura , N.Mutagens‐carcinogens in foods, with special reference to highly mutagenic pyrolytic products in broiled foods . In“Origins of Human Cancer,” Book C , ed , Hiatt H. H. , Watson J. D. and Winstein J. A. , pp. 1561 – 1577 ( 1977. ). Cold Spring Harbor Laboratory; , New York . [Google Scholar]
- 12. ) Takayama , S. , Nakatsuru , Y. and Sato , S.Carcinogenic effect of the simultaneous administration of five heterocyclic amines to F344 rats . Jpn. J. Cancer Res. (Gann) , 78 , 1068 – 1072 ( 1987. ). [PubMed] [Google Scholar]
- 13. ) Kasai , H. , Yamaizumi , Z. , Wakabayash , K. , Nagao , M. , Sugimura , T. , Yokoyama , S. , Miyazawa , T. , Springarn , N. E. , Weisburger , J. H. and Nishimura , S.Potent novel mutants produced by broiling fish under normal conditions . Proc. Jpn. Acad. , 56B , 278 – 278 ( 1980. ). [Google Scholar]
- 14. ) Kasai , H. , Nishimura , S. , Wakabayashi , K. , Nagao , M. and Sugimura , T.Chemical synthesis of 2‐amino‐3‐methylimidazo[4,5‐f]‐quinoline (IQ), a potent mutagen isolated from broiled fish . Proc. Jpn. Acad. , 56B , 382 – 382 ( 1980. ). [Google Scholar]
- 15. ) Yamazoe , Y. , Shimada , M. , Kamataki , T. and 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. , 43 , 5768 – 5774 ( 1983. ). [PubMed] [Google Scholar]
- 16. ) Barnes , W. S. , Lovelette , C. A. , Tong , C. , Williams , G. M. and Weisburger , J. H.Genotoxicity of the food mutagen 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) and analogs . Carcinogenesis , 6 , 441 – 444 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Loury , D. J. and Byard , J. L.Genotoxicity of the cooked‐food mutagens IQ and MelQ in primary cultures of rat, hamster, and guinea‐pig hepatocytes . Environ. Mutag. , 7 , 245 – 254 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 18. ) Ishikawa , T. , Takayama , S. , Kitagawa , T. , Kawachi , T. and Sugimura , T.Induction of enzyme‐altered islands in rat liver by tryptophan pyrolysis products . J. Cancer Res. Clin. Oncol. , 95 , 221 – 224 ( 1978. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Kitagawa , T. , Hirakawa , T. , Ishikawa , T. , Nemoto , N. and Takayama , S.Induction of hepatocellular carcinoma in rat liver by initial treatment with benzo(a)pyrene after partial hepatectomy and promotion by phenobarbital . Toxicol. Lett. , 6 , 167 – 171 ( 1980. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Ogiso , T. , Tatematsu , M. , Tamano , S. , Tsuda , H. and Ito , N.Comparative effects of carcinogens on the induction of placental glutathione S‐transferase‐positive liver nodules in a short‐term assay and of hepatocellular carcinoma in a long‐term assay . Toxicol. Pathol. , 13 , 257 – 265 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Tatematsu , M. , Mera , Y. , Ito , N. , Satoh , K. and Sato , K.Relative merits of immunohistochemical demonstrations of placental, A, B and C forms of glutathione S‐transferase and histochemical demonstration of gamma glutamyltranspeptidase as markers of altered foci during liver Carcinogenesis in rats . Carcinogenesis , 6 , 1621 – 1626 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Satoh , K. , Kitahara , A. , Soma , Y. , Inaba , Y. , Hatayama , I. and Sato , K.Purification, induction, and distribution of placental glutathione transferase: a new marker enzyme for preneoplastic cells in the rat chemical hepatocarcinogenesis . Proc. Natl. Acad. Sci. USA , 82 , 3964 – 3968 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23. ) Hsu , S. M. , Raine , L. and Farger , H.Use of avidin‐biotin‐peroxidase complex (ABC) in immunohistochemical techniques: a comparison between ABC and unlabelled antibody PAP procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Ishikawa , T. , Takayama , S. and Kitagawa , T.Correlation between time of partial hepatectomy after a single treatment with diethylnitrosamine and induction of adenosine triphosphatase‐deficient islands in rat liver . Cancer Res. , 40 , 4361 – 4361 ( 1980. ). [PubMed] [Google Scholar]
- 25. ) Hasegawa , R. , Tsuda , H. , Shirai , T. , Kurata , Y. , Masuda , A. and Ito , N.Effect of timing of partial hepatectomy on the induction of preneoplastic liver foci in rats given hepatocarcinogens . Cancer Lett. , 32 , 15 – 23 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 26. ) Tamano , S. , Tsuda , H. , Tatematsu , M. , Hasegawa , R. , Imaida , K. and Ito , N.Induction of γ‐glutamyl transpeptidase positive foci in rat liver by pyrolysis products of amino acids . Gann , 72 , 747 – 753 ( 1981. ). [PubMed] [Google Scholar]
- 27. ) Hasegawa , R. , Tsuda , H. , Ogiso , T. , Ohshima , M. and Ito , N.Initiating activities of pyrolysis products of L‐lysine and soybean globulin assessed in terms of the induction of gamma glutamyltranspeptidase‐positive foci in rat liver . Gann , 73 , 158 – 159 ( 1982. ). [PubMed] [Google Scholar]
- 28. ) Ito , N. , Tsuda , H. , Tatematsu , M. , Inoue , T. , Tagawa , Y. , Aoki , T. , Uwagawa , S. , Kagawa , M. , Ogiso , T. , Masui , T. , Imaida , K. , Fukushima , S. and Asamoto , M.Enhancing effect of various hepatocarcinogens on induction of preneoplastic glutathione S‐transferase placental form positive foci in rats — an approach for a new medium term bioassay system . Carcinogenesis , 9 , 387 – 394 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 29. ) IARC . IARC Monographs on the evaluation of the carcinogenic risk of chemicals to humans . Vol. 40 , 223 – 288 ( 1986. ). Oxford University Press; , London . [PubMed] [Google Scholar]
- 30. ) Pitot , H. C. , Goldworthy , T. L. , Moran , S. , Kennan , W. , Glauert , H. P. , Maronpot , R. R. and Campbell , H. A.A method to quantitate the relative initiating and promoting potencies of hepatocarcinogenic agents in their dose‐response relationships to altered hepatic foci . Carcinogenesis , 8 , 1491 – 1500 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 31. ) Nakanishi , K. , Fukushima , S. , Hagiwara , A. , Tamano , S. and Ito , N.Organ‐specific promoting effects of phenobarbital sodium and sodium saccharin in the induction of liver and urinary bladder tumors in male F344 rats . J. Natl. Cancer Inst. , 68 , 497 – 500 ( 1982. ). [PubMed] [Google Scholar]
- 32. ) Shirai , T. , Imaida , K. , Ohshima , M. , Fukushima , S. , Lee , M‐S. , King , C. M. and Ito , N.Different responses to phenobarbital promotion in the development of γ‐glutamyltranspeptidase‐positive foci in the liver of rats initiated with diethylnitrosamine, N‐hydroxy‐2‐acetylaminofluorene and aflatoxin B1 , Jpn. J. Cancer Res. (Gann) , 76 , 16 – 16 ( 1985. ). [PubMed] [Google Scholar]
- 33. ) Ito , N.Organ‐specific modifying effects of phenobarbital, saccharin and antioxidants on 2‐stage chemical Carcinogenesis . In “ New Concepts and Developments in Toxicology ,” ed. Chambers P. L. , Gehring P. and Sakai F. , pp. 359 – 369 ( 1986. ). Elsevier Science Publishers B. V. , Amsterdam . [PubMed] [Google Scholar]
- 34. ) Hiasa , Y. , Kitahori , Y. , Ohshima , M. , Fujita , Y. , Yuasa , T. , Konishi , N. and Miyasato , A.Promoting effects of phenobarbital and barbital on development of thyroid tumors in rats treated with N‐bis(2‐hydroxypropyl)‐nitrosamine . Carcinogenesis , 3 , 1187 – 1190 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 35. ) Tsuda , H. , Fukushima , S. , Imaida , K. , Kurata , Y. and Ito , N.Organ‐specific promoting effect of phenobarbital and saccharin in induction of thyroid, liver, and urinary bladder tumors in rats after initiation with N‐nitrosomethylurea . Cancer Res. , 43 , 3292 – 3296 ( 1983. ). [PubMed] [Google Scholar]