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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1992 Oct;83(10):1047–1051. doi: 10.1111/j.1349-7006.1992.tb02720.x

Species Difference among Experimental Rodents in Induction of P450IA Family Enzymes by 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine

Masakuni Degawa 1, Ken‐ichiro Kobayashi 1, Shin‐ichi Miura 1, Hiroshi Arai 1, Hiroyasu Esumi 2, Takashi Sugimura 2, Yoshiyuki Hashimoto 1,
PMCID: PMC5918673  PMID: 1452456

Abstract

Rats, mice, hamsters and guinea pigs were given an i.p. injection of 2‐amino‐1‐methyl‐6‐phenyl‐imidazo[4,5‐b]pyridine (PhIP), a protein‐derived pyrolysate component present in cooked foods, and inductions of cytochrome P450 (P450) in the liver and kidney of these animals were examined. The activity and amount of P450s corresponding to the rat P4S0IA1 and P450IA2 were assessed by means of a bacterial mutation test using 3 carcinogenic heterocyclic aromatic amines including PhIP as substrates and by Western blotting with a monoclonal antibody reactive with both P4S0IA1 and P450IA2. In rats, PhIP induced P450IA1, P450IA2 and a new but unspecified P450 isozyme in the liver, and induced P450IA1 in the kidney. However, PhIP induced none of these P450 isozymes in mice, hamsters and guinea pigs.

Keywords: 2‐Amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine; PhIP; P450‐induction; Species difference; Rodent

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REFERENCES

  • 1. ) Degawa , M. , Agatsuma , T. and Hashimoto , Y.Species difference among experimental rodents in the activity and induction of cytochrome P‐450 isozymes for mutagenic activation of carcinogenic aromatic amines . Jpn. J. Cancer Res. , 81 , 1253 – 1258 ( 1990. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2. ) Degawa , M. , Hishinuma , T. , Yoshida , H. and Hashimoto , Y.Species, sex and organ differences in induction of a cytochrome P‐450 isozyme responsible for carcinogen activation: effects of dietary hepatocarcinogenic tryptophan pyrolysate components in mice and rats . Carcinogenesis , 8 , 1913 – 1918 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 3. ) Degawa , M. , Yamada , H. , Hishinuma , T. , Masuko , T. and Hashimoto , Y.Organ selective induction of cytochrome P‐448 isozymes in the rat by 2‐methoxy‐4‐aminoazoben‐zene and 3‐methylcholanthrene . J. Biochem. , 101 , 1437 – 1445 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 4. ) Degawa , M. , Miura , S. and Hashimoto , Y.Androgen‐dependent renal microsomal cytochrome P‐450 responsible for N‐hydroxylation and mutagenic activation of 3‐methoxy‐4‐aminoazobenzene in mice . Cancer Res. , 50 , 2729 – 2733 ( 1990. ). [PubMed] [Google Scholar]
  • 5. ) Gonzalez , F. J.The molecular biology of cytochrome P‐450s . Pharmacol. Rev. , 40 , 243 – 288 ( 1989. ). [PubMed] [Google Scholar]
  • 6. ) Goldstein , J. A. and Linko , P.Differential induction of two 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐inducible forms of cytochrome P‐450 in extrahepatic versus hepatic tissues . Mol. Pharmacol. , 25 , 185 – 191 ( 1984. ). [PubMed] [Google Scholar]
  • 7. ) Okey , A. B.Enzyme induction in the cytochrome P‐450 system . Pharmacol. Ther. , 45 , 241 – 289 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 8. ) Miura , S. , Degawa , M. and Hashimoto , Y.Renal and hepatic microsomal enzymes responsible for bioactivation of 3‐methoxy‐4‐aminoazobenzene in the rodent . Biochem. Pharmacol. , 42 , 1655 – 1659 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 9. ) Degawa , M. , Kojima , M. and Hashimoto , Y.Species difference between rats and mice in activities of enzymes activating aromatic amines: effect of dietary 3‐methoxy‐4‐aminoazobenzene . Gann , 75 , 966 – 975 ( 1984. ). [PubMed] [Google Scholar]
  • 10. ) Degawa , M. , Kojima , M. , Hishinuma , T. and Hashimoto , Y.Sex‐dependent induction of hepatic enzymes for mutagenic activation of a tryptophan pyrolysate component, 3‐amino‐l,4‐dimethyl‐5H‐pyrido[4,3‐b]indole, by feeding in mice . Cancer Res. , 45 , 96 – 102 ( 1985. ). [PubMed] [Google Scholar]
  • 11. ) Degawa , M. , Kojima , M. , Sato , Y. and Hashimoto , Y.Induction of a high spin form of microsomal cytochrome P‐448 in rat liver by 4‐aminoazobenzene derivatives . Biochem. Pharmacol. , 35 , 3565 – 3570 ( 1986. ). [DOI] [PubMed] [Google Scholar]
  • 12. ) Degawa , M. , Tanimura , S. , Agatsuma , T. and Hashimoto , Y.Hepatocarcinogenic heterocyclic aromatic amines that induce cytochrome P‐448 isozymes, mainly cytochrome P‐448H (P‐450IA2), responsible for mutagenic activation of the carcinogens in rat liver . Carcinogenesis , 10 , 1119 – 1122 ( 1989. ). [DOI] [PubMed] [Google Scholar]
  • 13. ) Felton , J. S. , Knize , M. G. , Shen , N. H. , Andersen , B. D. , Bjeldanes , L. F. and Hatch , F. T.Identification of the mutagens in cooked beef . Environ. Health Perspect. , 67 , 17 – 24 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 14. ) Shioya , M. , Wakabayashi , K. , Sato , S. , Nagao , M. and Sugimura , T.Formation of a mutagen, 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) in cooked beef, by heating a mixture containing creatine, phenylalanine and glucose . Mutat. Res. , 191 , 133 – 138 ( 1987. ). [DOI] [PubMed] [Google Scholar]
  • 15. ) 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]
  • 16. ) Manabe , S. , Tohyama , K. , Wada , O. and Aramaki , T.Detection of a carcinogen, 2‐amino‐1‐methyl‐6‐phenyl‐imidazo[4,5‐b]pyridine (PhIP) in cigarette smoke condensate . Carcinogenesis , 12 , 1945 – 1948 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 17. ) Esumi , H. , Ohgaki , H. , Kohzen , E. , Takayama , S. and Sugimura , T.Induction of lymphoma in CDF, mice by the food mutagen, 2‐amino‐1‐methyl‐6‐phenylimidazo [4,5‐b]‐pyridine . Jpn. J. Cancer Res. , 80 , 1176 – 1178 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18. ) 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]
  • 19. ) Wallin , H. , Mikalsen , A. , Guengerich F. P. , Ingelman‐Sundberg , M. , Solberg , K. E. , Rossland , O. J. and Alexander , J.Differential rates of metabolic activation and detoxication of the food mutagen 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine by different cytochrome P450 enzymes . Carcinogenesis , 11 , 489 – 492 ( 1990. ). [DOI] [PubMed] [Google Scholar]
  • 20. ) Adachi , H. , Degawa , M. , Miura , S. , Hashimoto , Y. , Sugimura , T. and Esumi , H.Induction of putative new cytochrome P‐450 isozyme in rat liver by 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine . Biochem Biophys. Res. Commun. , 174 , 797 – 803 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 21. ) Watkins , B. E. , Esumi , H. , Wakabayashi , K. , Nagao , M. and Sugimura , T.Fate and distribution of 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyndine (PhIP) in rats . Carcinogenesis , 12 , 1073 – 1078 ( 1991. ). [DOI] [PubMed] [Google Scholar]
  • 22. ) Lowry , O. H. , Rosebrough , N. J. , Farr , A. L. and Randall , R. J.Protein measurement with the Folin phenol reagent . J. Biol Chem. , 193 , 265 – 275 ( 1951. ). [PubMed] [Google Scholar]
  • 23. ) Omura , T. and Sato , R.The carbon monooxide binding pigment of liver microsomes. I. Evidence for its hemoprotein nature . J. Biol. Chem. , 239 , 2370 – 2378 ( 1964. ). [PubMed] [Google Scholar]
  • 24. ) Degawa , M. , Ueno , H. , Miura , S. , Ohta , A. and Namiki , M.A simple method for assessment of rat cytochrome P‐448 isozymes responsible for the mutagenic activation of carcinogenic chemicals . Mutat. Res. , 203 , 333 – 338 ( 1988. ). [DOI] [PubMed] [Google Scholar]
  • 25. ) Kamataki , T. , Maeda , K. , Yamazoe , Y. , Matsuda , N. , Ishii , K. and Kato , R.A high spin of cytochrome P‐450 highly purified from PCB‐treated rats: catalytic characterization and immunochemical quantitation in liver microsomes . Mol. Pharmacol. , 24 , 146 – 155 ( 1983. ). [PubMed] [Google Scholar]
  • 26. ) Degawa , M. , Ohta , A. , Namiki , M. , Masuko , T. and Hashimoto , Y.In vivo selection of a low spin form of cytochrome P‐448 from 3‐methylcholanthrene‐induced rat cytochrome P‐450 isozymes by carbon tetrachloride . Biochem. Pharmacol. , 36 , 3315 – 3317 ( 1987. ). [DOI] [PubMed] [Google Scholar]

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