Roles of different cytochrome P-450 enzymes in bioactivation of the hepatocarcinogen 3-methoxy-4-aminoazobenzene by rat and human liver microsomes

Conference · Mon Mar 11 00:00:00 EST 1991 · FASEB Journal (Federation of American Societies for Experimental Biology); (United States)

OSTI ID:5696125

Shimada, T; Yamazaki, H; Degawa, M; Funae, Y; Imaoka, S; Inui, Y; Guengerich, F P ^[1]

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1. Osaka Prefectual Inst. of Public Health, Nakamichi, Higashinariku (Japan) Tohoku Univ., Aobayama (Japan) Osaka City Univ., Abenoku (Japan) Center for Adult Diseases, Nakamichi, Higashinariku, Osaka (Japan) Vanderbilt Univ., Nashville, TN (United States)

The potent hepatocarcinogen 3-methoxy-4-aminoazobenzene (3-MeO-AAB) has been reported to be bioactivated to mutagenic intermediates by rat liver microsomal cytochrome P-450 (P-450) and to be a selective inducer of rat P-450IA2. 3-MeO-AAB was found to be bioactivated by liver microsomal enzymes from rats and humans in a Salmonella typhimurium TA1535/pSK1002 system where umu response is indicative of DNA damage. The liver microsomal activities are increased by pretreatment of rats with various P-450 inducers. Evidence has also been obtained that specific antibodies raised against P-4502B1, P-4501A1 or 1A2, P-4502E1, and P4503A inhibited the activation in rat liver microsomes suggesting the possible roles of several P-450 enzymes in the bioactivation of 3-MeO-AAB, and results obtained with various purified rat P-450 enzymes support this view. Human liver microsomal activation of 3-MeO-AAB was also inhibited to various extents by antibodies raised against P-4501A, P-4502C, P-4502E1, and P-4503A enzymes. Purified P-4501A2 was the most active human P-450 in oxidizing 3-MeO-AAB, followed by P-4503A4 and P-450{sub MP} (P4502C). From these results it is concluded that multiple P-450 enzymes in rat and human liver microsomes are involved in the bioactivation of 3-MeO-AAB, regardless of its selective induction of the P4501A2 gene.

• OSTI ID: 5696125
• Report Number(s): CONF-9104107-; CODEN: FAJOE
• Journal Information: FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Vol. 5:4; Conference: 75. annual meeting of the Federation of American Societies for Experimental Biology (FASEB), Atlanta, GA (United States), 21-25 Apr 1991; ISSN 0892-6638
• Country of Publication: United States
• Language: English

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