Abstract
2‐Amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP), the most abundant mutagenic heterocyclic amine in cooked foods, was examined for carcinogenic potential using Nagase analbuminemic rats (NARs), which are sensitive to various carcinogens. The concentration of PhIP in the diet was 0.04% at the beginning of the experiment, this being subsequently gradually reduced to 0.01% to avoid severe body weight loss. Ten of 13 treated NARs developed a total of 36 intestinal tumors within the 311‐day experimental period. Among these, 22 were adenocarcinomas and 2 were adenomas of the small intestine, 4 were adenocarcinomas of the cecum and 8 were adenocarcinomas of the large intestine. The results suggest that PhIP could represent a significant risk to human populations exposed to foods containing heterocyclic amines.
Keywords: Mutagen in food, Heterocyclic amine
Full Text
The Full Text of this article is available as a PDF (236.3 KB).
REFERENCES
- 1. ) 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]
- 2. ) Becher , G. , Knize , M. G. , Nes , I. F. and Felton , J. S.Isolation and identification of mutagens from a fried Norwegian meat product . Carcinogenesis , 9 , 247 – 253 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 3. ) Zhang , X‐M. , Wakabayashi , K. , Liu , Z‐C. , Sugimura , T. and Nagao , M.Mutagenic and carcinogenic heterocyclic amines in Chinese cooked foods . Mutat. Res. , 201 , 181 – 188 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Sugimura , T.New environmental carcinogens in daily life . Trends Pharmacol. Sci. , 9 , 205 – 209 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Sugimura , T. , Wakabayashi , K. , Nagao , M. and Ohgaki , H.Heterocyclic amines in cooked food . In “ Food Toxicology: A Perspective on the Relative Risks ”, ed. L S. L. and Scanlan R. A. , pp. 31 – 55 ( 1989. ). Marcel Dekker, Inc. , New York and Basel . [Google Scholar]
- 6. ) Thompson , L. H. , Tucker , J. D. , Stewart , S. A. , Christensen , M. L. , Salazar , E. P. , Carrano , A. V. and Felton , J. S.Genotoxicity of compounds from cooked beef in repair‐deficient CHO cells versus Salmonella mutagenicity . Mutagenesis , 2 , 483 – 487 ( 1987. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Esumi , H. , Ohgaki , H. , Kohzen , E. , Takayama , S. and Sugimura , T.Induction of lymphoma in CDF1 mice by the food mutagen, 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]‐pyridine . Jpn. J. Cancer Res. , 80 , 1176 – 1178 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Takayama , K. , Yamashita , K. , Wakabayashi , K. , Sugimura , T. and Nagao , M.DNA modification by 2‐amino‐l‐methyl‐6‐phenylimidazo[4,5‐b]pyridine in rats . Jpn. J. Cancer Res. , 80 , 1145 – 1148 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9. ) 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]
- 10. ) Nagase , S. , Shimamune , K. and Shumiya , S.Albumin deficient rat mutant . Science , 205 , 590 – 591 ( 1979. ). [DOI] [PubMed] [Google Scholar]
- 11. ) Kakizoe , T. and Sugimura , T.Chemical carcinogenesis in analbuminemic rats . Jpn. J. Cancer Res. , 79 , 775 – 784 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12. ) Hosaka , Y. , Muramatsu , M. , Matsushima , T. , Niijima , T. and Nagase , S.Low susceptibility of analbuminemic rats to induction of bladder cancer by N‐[4‐(5‐nitro‐2‐furyl)‐2‐thiazolyl] formamide . Jpn. J. Cancer Res. , 76 , 577 – 582 ( 1985. ). [PubMed] [Google Scholar]
- 13. ) Ochiai , M. , Takayama , K. , Takayama , S. , Nagase , S. , Sugimura , T. and Nagao , M.High susceptibility of F344‐analbuminemic rat to the intestinal carcinogenesis induced by IQ . Proc. Jpn. Cancer Assoc. 48th Annu. Meet. , 81 ( 1989. ) ( in Japanese ). [Google Scholar]
- 14. ) Takikawa , H. , Seyama , Y. , Sugiyama , Y. and Nagase , S.Bile acid profiles in analbuminemia rats . J. Biochem. , 97 , 199 – 203 ( 1985. ). [DOI] [PubMed] [Google Scholar]