Skip to main content
Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1994 May;85(5):510–514. doi: 10.1111/j.1349-7006.1994.tb02388.x

Absence of p53 Mutations in Rat Colon Tumors Induced by 2‐Amino‐6‐methyldipyrido[1,2‐a:3′, 2′‐d]imidazole, 2‐Amino‐3‐methylimidazo[4,5‐f]quinoline, or 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Hiroshi Makino 1, Toshikazu Ushijima 1, Hideki Kakiuchi 1, Masahiko Onda 2, Nobuyuki Ito 3, Takashi Sugimura 1, Minako Nagao 1
PMCID: PMC5919493  PMID: 8014110

Abstract

Colon tumors were induced in F344 rats by three heterocyclic amines (HCAs), 2‐amino‐6‐methyl‐dipyrido[1,2‐a:3′, 2′‐d]imidazole (Glu‐P‐1), 2‐amino‐3‐methylimidazo[4,5‐f]quinoline (IQ) or 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), and examined for p53 mutations. Seven carcinomas induced by Glu‐P‐1, and nine carcinomas and two adenomas induced by IQ were examined by cDNA‐polymerase chain reaction‐single strand conformation polymorphism (PCR‐SSCP) analysis from codon 103 to 391 of p53, which encompasses the conserved regions II to IV. Nine carcinomas induced by PhIP were examined by genomic PCR‐SSCP analysis of exons 5 to 7 (from codon 124 to 304), which encompasses the 3’half of the conserved region II and all the conserved regions III‐V. No band shifts were found in any of these tumors under at least two conditions of SSCP analysis. Our previous study had shown a Ki‐ras mutation in only one Glu‐P‐1‐induced adenocarcinoma among the same 27 colon tumors, and no other mutation of ras family genes had been found. HCA‐induced rat colon tumors appear to represent a group of human colon tumors in which neither Ki‐ras nor p53 is involved.

Keywords: Heterocyclic amine, Genetic alteration, Chemically induced tumor, Colorectal neoplasm

Full Text

The Full Text of this article is available as a PDF (314.4 KB).

REFERENCES

  • 1. ) Wakabayashi , K. , Nagao , M. , Esumi , H. and Sugimura , T.Food‐derived mutagens and carcinogens . Cancer Res. , 52 , 2092s – 2098s ( 1992. ). [PubMed] [Google Scholar]
  • 2. ) Yamamoto , T. , Tsuji , K. , Kosuge , T. , Okamoto , T. , Shudo , K. , Takeda , K. , Iitaka , Y. , Yamaguchi , K. , Seino , Y. , Yahagi , T. , Nagao , M. and Sugimura , T.Isolation and structure determination of mutagenic substances in L‐glutaminic acid pyrolysate . Proc. Jpn. Acad. , 54 , 248 – 250 ( 1978. ). [Google Scholar]
  • 3. ) Kasai , H. , Yamaizumi , Z. , Wakabayashi , K. , Nagao , M. , Sugimura , T. , Yokoyama , S. , Miyazawa , T. , Springarn , N. E. , Weisburger , J. H. and Nishimura , S.Potent novel mutagen produced by broiling fish under normal conditions . Proc. Jpn. Acad. , 56B , 278 – 283 ( 1980. ). [Google Scholar]
  • 4. ) Yamashita , M. , Wakabayashi , K. , Nagao , M. , Sato , S. , Yamaizumi , Z. , Takahashi , M. , Kinae , N. , Tomita , I. and Sugimura , T.Detection of 2‐amino‐3‐methylimidazo‐[4,5‐f]quinoline in cigarette smoke condensate . Jpn. J. Cancer Res. , 77 , 419 – 422 ( 1986. ). [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. ) 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]
  • 7. ) Felton , J. S. , Knize , M. G. , Shen , N. H. , Lewis , P. R. , Andresen , B. D. , Happe , J. and Hatch , F. T.The isolation and identification of a new mutagen from fried ground beef: 2‐amino‐1‐methyl‐ 6‐phenylimidazo [4,5‐b] pyridine (PhIP) . Carcinogenesis , 7 , 1081 – 1086 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Ito , N. , Hasegawa , R. , Sano , M. , Tamano , S. , Esumi , H. , Takayama , S. and Sugimura , T.A new colon and mammary carcinogen in cooked food, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) . Carcinogenesis , 12 , 1503 – 1506 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Vogelstein , B. and Kinzler , K. W.Carcinogens leave fingerprints . Nature , 355 , 209 – 210 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 10. ) Vogelstein , B. , Fearon , E. R. , Hamilton , S. R. , Kern , S. E. , Preisinger , A. C. , Leppert , M. , Nakamura , Y. , White , R. , Smits , A. M. M. and Bos , J. L.Genetic alterations during colorectal‐tumor development . N. Engl. J. Med. , 319 , 525 – 532 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 11. ) Fearon , E. R. and Vogelstein , B.A genetic model for colorectal tumorigenesis . Cell , 61 , 759 – 767 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Ichii , S. , Takeda , S. , Horii , A. , Nakatsuru , S. , Miyoshi , Y. , Emi , M. , Fujiwara , Y. , Koyama , K. , Furuyama , J. , Utsunomiya , J. and Nakamura , Y.Detailed analysis of genetic alterations in colorectal tumors from patients with and without familial adenomatous polyposis (FAP) . Oncogene , 8 , 2399 – 2405 ( 1993. ). [PubMed] [Google Scholar]
  • 13. ) Kakiuchi , H. , Ushijima , T. , Makino , H. , Ishizaka , Y. , Hasegawa , R. , Ito , N. , Sugimura , T. and Nagao , M.Rare frequency of activation of Ki‐ras in rat colon carcinomas induced by heterocyclic amines, suggesting alternative mechanisms of human colon carcinogenesis . Mol. Carcinog. , 8 , 44 – 48 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 14. ) Makino , H. , Ishizaka , Y. , Tsujimoto , A. , Nakamura , T. , Onda , M. , Sugimura , T. and Nagao , M.Rat p53 gene mutations in primary Zymbal gland tumors induced by 2‐amino‐3‐methylimidazo[4,5‐f]quinoline, a food mutagen . Proc. Natl. Acad. Sci. USA , 89 , 4850 – 4854 ( 1992. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. ) Chomczynski , P. and Sacchi , N.Single‐step method of RNA isolation by acid guanidinium thiocyanate‐phenol‐chloroform extraction . Anal. Biochem. , 162 , 156 – 159 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 16. ) Impraim , C. C. , Saiki , R. K. , Erlich , H. A. and Teplitz , R. L.Analysis of DNA extracted from formalin‐fixed, paraffin‐embedded tissues by enzymatic amplification and hybridization with sequence‐specific oligonucleotides . Biochem. Biophys. Res. Commun. , 142 , 710 – 716 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Orita , M. , Iwahana , H. , Kanazawa , H. , Hayashi , K. and Sekiya , T.Detection of polymorphisms of human DNA by gel electrophoresis as single‐strand conformation polymorphisms . Proc. Natl. Acad. Sci. USA , 86 , 7652 – 7656 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) Hulla , J. E. and Schneider , R. P.Structure of the rat p53 tumor suppressor gene . Nucleic Acids Res. , 21 , 713 – 717 ( 1993. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 19. ) Hayashi , K.PCR‐SSCP: a simple and sensitive method for detection of mutations in the genomic DNA . PCR Methods Appl. , 1 , 34 – 38 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Hayashi , K. and Yandell , D. W.How sensitive is PCR‐SSCP ? Hum. Mutat. , 2 , 338 – 346 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Ushijima , T. , Makino , H. , Kakiuchi , H. , Inoue , R. , Tsujimoto , A. , Sugimura , T. and Nagao , M.Genetic alterations in HCA‐induced tumors . Proc. 23rd Int. Symp. Princess Takamatsu Cancer Res. Fund , ( 1993. ), in press . [PubMed] [Google Scholar]
  • 22. ) Caron de Fromental , C. and Soussi , T.TP53 tumor suppressor gene: a model for investigating human mutagenesis . Genes Chromosomes Cancer , 4 , 1 – 15 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 23. ) Muto , T. , Bussey , H. J. R. and Morson , B. C.The evolution of cancer of the colon and rectum . Cancer , 36 , 2251 – 2270 ( 1975. ). [DOI] [PubMed] [Google Scholar]
  • 24. ) Baker , S. J. , Preisinger , A. C. , Jessup , J. M. , Paraskeva , C. , Markowitz , S. , Willson , J. K. , Hamilton , S. and Vogelstein , B.p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis . Cancer Res. , 50 , 7717 – 7722 ( 1990. ). [PubMed] [Google Scholar]
  • 25. ) Smith , M. L. , Yeleswarapu , L. , Scalamogna , P. , Locker , J. and Lombardi , B.p53 mutations in hepatocellular carcinomas induced by a choline‐devoid diet in male Fischer 344 rats . Carcinogenesis , 14 , 503 – 510 ( 1993. ). [DOI] [PubMed] [Google Scholar]
  • 26. ) Recio , L. , Sisk , S. , Pluta , L. , Bermudez , E. , Gross , E. A. , Chen , Z. , Morgan , K. and Walker , C.p53 mutations in formaldehyde‐induced nasal squamous cell carcinomas in rats . Cancer Res. , 52 , 6113 – 6116 ( 1992. ). [PubMed] [Google Scholar]
  • 27. ) Jacoby , R. F. , Llor , X. , Teng , B. B. , Davidson , N. O. and Brasitus , T. A.Mutations in the K‐ras oncogene induced by 1,2‐dimethylhydrazine in preneoplastic and neoplastic rat colonic mucosa . J. Clin. Invest. , 87 , 624 – 630 ( 1991. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28. ) Jacoby , R. F. , Alexander , R. J. , Raicht , R. F. and Brasitus , T.K‐ras oncogene mutations in rat colon tumors induced by N‐methyl‐N‐nitrosourea . Carcinogenesis , 13 , 45 – 49 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 29. ) Llor , X. , Jacoby , R. F. , Teng , B. B. , Davidson , N. O. , Sitrin , M. D. and Brasitus , T. A.K‐ras mutations in 1,2‐dimethylhydrazine‐induced colonic tumors: effects of supplemental dietary calcium and vitamin D deficiency . Cancer Res. , 51 , 4305 – 4309 ( 1991. ). [PubMed] [Google Scholar]
  • 30. ) Stopera , S. A. , Murphy , L. C. and Bird , R. P.Evidence for a ras gene mutation in azoxymethane‐induced colonic aberrant crypts in Sprague‐Dawley rats: earliest recognizable precursor lesions of experimental colon cancer . Carcinogenesis , 13 , 2081 – 2085 ( 1992. ). [DOI] [PubMed] [Google Scholar]
  • 31. ) Su , L.‐K. , Kinzler , K. , Vogelstein , B. , Preisinger , A. C. , Moser , A. R. , Luongo , C. , Gould , K. A. and Dove , W. F.Multiple intestinal neoplasia caused by a mutation in the murine homologue of the APC gene . Science , 256 , 668 – 670 ( 1992. ). [DOI] [PubMed] [Google Scholar]

Articles from Japanese Journal of Cancer Research : Gann are provided here courtesy of Wiley

RESOURCES