Abstract
The expression of cytochrome P450 3A4 (CYP3A4) in the foveolar epithelium of the human stomach with intestinal metaplasia was studied using immunohistochemistry, western blotting and reverse transcription polymerase chain reaction (RT‐PCR). CYP3A4 was immunohistochemically detected in the foveolar epithelium with intestinal metaplasia, but was not detected in foveolar epithelium without intestinal metaplasia, in the pyloric gland or in the fundic gland of the stomach. Western blotting and RT‐PCR demonstrated that CYP3A4 protein and mRNA were expressed in the liver and pyloric gland mucosa with intestinal metaplasia, but not in the fundic gland mucosa without intestinal metaplasia. Possible roles of CYP expression in the gastric mucosa with intestinal metaplasia in human stomach carcinogenesis are briefly discussed.
Keywords: Human, Stomach, Cytochrome P450 3A4, Intestinal metaplasia, Reverse transcription polymerase chain reaction
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REFERENCES
- 1. ) Nelson , D. R. , Kamataki , T. , Waxman , D. J. , Guengerich , F. P. , Estabrook , R. W. , Feyereisen , R. , Gonzalez , F. J. , Coon , M. J. , Gunsalus , I. C. , Gotoh , O. , Okuda , K. and Nebert , D. W.The P450 superfamily: update on new sequences, gene mapping, accession numbers, early trivial names of enzymes, and nomenclature . DNA Cell Biol. , 12 , 1 – 51 ( 1993. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Degawa , M. , Stern , S. J. , Martin , M. V. , Guengerich , F. P. , Fu , P. P. , Ilett , K. F. , Kaderlik , R. K. and Kadlubar , F. F.Metabolic activation and carcinogen‐DNA adduct detection in human larynx . Cancer Res. , 54 , 4915 – 4919 ( 1994. ). [PubMed] [Google Scholar]
- 3. ) Kivistoe , K. T. , Fritz , P. , Linder , A. , Friedel , G. , Beaune , P. and Kroemer , H. K.Immunohistochemical localization of cytochrome P450 3A in human pulmonary carcinomas and normal bronchial tissue . Histochemistry , 103 , 25 – 29 ( 1995. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Murray , M. and Reidy , G. F.Selectivity in the inhibition of mammalian cytochrome P‐450 by chemical agents . Pharmacol. Rev. , 42 , 85 – 101 ( 1990. ). [PubMed] [Google Scholar]
- 5. ) Watkins , P. B. , Wrighton , S. A. , Maurel , P. , Schetz , E. G. , Mendez‐Picon , G. , Parker , G. A. and Guzelian , P. S.Identification of an inducible form of cytochrome P‐450 in human liver . Proc. Natl. Acad. Sci. USA , 82 , 6310 – 6314 ( 1985. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6. ) Miura , S. M. , Mori , M. , Takiguchi , M. , Tatibana , M. , Furuta , S. , Miyazawa , S. and Hashimoto , T.Biosynthesis and intracellular transport of enzymes of peroxisomal beta‐oxidation . J. Biol. Chem. , 259 , 6397 – 6402 ( 1984. ). [PubMed] [Google Scholar]
- 7. ) Peers , F. G. and Linsell , C. A.Dietary aflatoxins and liver cancer: population based study in Kenya . Br. J. Cancer , 27 , 473 – 481 ( 1973. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Shank , R. C. , Bhamarapravati , N. , Gordon , J. E. and Wogan , G. N.Dietary aflatoxins and human liver cancer (IV): incidence in Thailand . Food Cosmet. Toxicol. , 10 , 171 – 179 ( 1972. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Hirota , T. , Okada , T. , Itabashi , M. , Yoshida , H. , Matsukura , H. , Kitaoka , H. and Hirayama , T.Significance of intestinal metaplasia as a precancerous condition of the stomach . In“Precursors of Gastric Cancer ,” ed. Ming S. C. , pp. 179 – 193 ( 1984. ). Praeger; , New York . [Google Scholar]
- 10. ) Matsukura , N. , Suzuki , K. , Kawachi , T. , Aoyagi , M. , Sugimura , T. , Kitaoka , H. , Numajiri , H. , Shirota , A. , Itabashi , M. and Hirota , T.Distribution of marker enzymes and mucin in intestinal metaplasia in human stomachs and relation of complete and incomplete types of metaplasia to minute gastric carcinoma . J. Natl. Cancer Inst. , 65 , 231 – 240 ( 1980. ). [PubMed] [Google Scholar]
- 11. ) Thummel , K. E. , O'Shea , D. , Paine , M. F. , Shen , D. D. , Kunze , K. L. , Perkins , J. D. and Wilkinson , G. R.Oral fast‐pass elimination of midazolam involves both gastrointestinal and hepatic CYPSA‐mediated metabolism . Clin. Pharmacol. Ther. , 59 , 491 – 502 ( 1996. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Guengerich , F. P.Roles of cytochrome P‐450 enzymes in chemical carcinogenesis and cancer chemotherapy . Cancer Res. , 48 , 2946 – 2954 ( 1988. ). [PubMed] [Google Scholar]
- 13. ) Hsu , S. M. , Raine , L. and Fange , H.Use of avidin‐biotin‐peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures . J. Histochem. Cytochem. , 29 , 577 – 580 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 14. ) Kremers , P. , Beaune , P. , Cresteil , T. , De Graeve , J. , Columelli , S. , Leroux , J. P. and Gielen , J. E.Cytochrome P‐450 monooxygenase activity in human and rat liver microsomes . Eur. J. Biochem. , 118 , 599 – 606 ( 1981. ). [DOI] [PubMed] [Google Scholar]
- 15. ) Laemmli , U. K.Cleavage of structural properties during the assembly of the head of bacteriophage T4 . Nature , 227 , 680 – 685 ( 1970. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Beaune , P. , Flinois , J. P. , Kiffel , L. , Kremers , P. and Leroux , J. P.Purification of a new cytochrome P 450 from human liver microsomes . Biochim. Biophys. Acta , 860 , 364 – 370 ( 1985. ). [DOI] [PubMed] [Google Scholar]
- 17. ) Noonan , K. E. and Robinson , I. B.mRNA phenotyping by enzymatic amplification of randomly primed cDNA . Nucleic Acids Res. , 16 , 10366 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 18. ) Gonzalez , F. J. , Schmid , B. J. , Umeno , M. , McBride , O. W. , Hardwick , J. P. , Meyer , U. A. , Gelboin , H. V. and Idle , J. R.Human p450PCN1: sequence, chromosomal localization, and direct evidence through cDNA expression that p450PCN1 is nifedipine oxidase . DNA , 7 , 79 – 86 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 19. ) Komori , M. , Nishio , K. , Ohi , H. , Kitada , M. and Katamiki , T.Molecular cloning and sequence analysis of cDNA containing the entire coding region for human fetal liver cytochrome p450 . J. Biochem. , 105 , 161 – 163 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 20. ) Molowa , D. T. , Schuetz , E. G. , Wrighton , S. A. , Watkins , P. B. , Kremers , P. , Mendez‐Picon , G. , Parler , G. A. and Guzelian , P. S.Complete cDNA sequence of a cytochrome P‐450 inducible by glucocorticoids in human liver . Proc. Natl. Acad. Sci. USA , 83 , 5311 – 5315 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 21. ) Murray , G. I. , Barnes , T. S. , Sewell , H. F. , Ewen , S. W. B. , Melvin , W. T. and Burke , M. D.The immunohistochemical localization and distribution of cytochrome P‐450 in normal human hepatic and extrahepatic tissues with monoclonal antibody to human cytochrome P‐450 . Br. J. Clin. Pharmacol. , 25 , 465 – 475 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 22. ) Kolars , J. C. , Lown , K. S. , Schmiedlin‐Ren , P. , Ghosh , M. , Fang , C. , Wrighton , S. A. , Merion , R. M. and Watkins , P. B.CYP3A gene expression in human gut epithelium . Pharmacogenetics , 4 , 247 – 259 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Lee , H. S. , Sarosi , I. and Vyas , G. N.Aflatoxin B1 form‐amidopyrimidine adducts in human hepatocarcinogenesis: a preliminary report . Gastroenterology , 97 , 1281 – 1287 ( 1989. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Stemmermann , G. N.Intestinal metaplasia of the stomach: a status report . Cancer , 74 , 556 – 564 ( 1994. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Ochiai , A. and Hirohashi , S.Genetic alterations in the precursors of gastric cancer . In“Molecular Pathology of Gastroenterological Cancer: Application to Clinical Practice ,” ed. Tahara E. , pp. 43 – 53 ( 1997. ). Springer‐Verlag; , Tokyo . [Google Scholar]
- 26. ) Kaminsky , L. S. and Fasco , M. J.Production and purification of antibodies to rat liver cytochrome P‐450 . Crit. Rev. Toxicol. , 21 , 407 – 422 ( 1992. ). [Google Scholar]
- 27. ) McKinnon , R. A. and McManus , M. E.Function and localization of cytochromes P450 involved in the metabolic activation of food‐derived heterocyclic amines . Proc. 23rd Int. Symp. Princess Takamatsu Cancer Res. Fund , 145 – 153 ( 1995. ). [PubMed]
- 28. ) Kolars , J. C. , Benedict , P. , Schmiedlin‐Ren , P. and Watkins , P. B.Aflatoxin B1‐adduct formation in rat and human small bowel enterocytes . Gastroenterology , 106 , 433 – 439 ( 1994. ). [DOI] [PubMed] [Google Scholar]