Organ selective induction of cytochrome P-448 isozymes in the rat by 2-methoxy-4-aminoazobenzene and 3-methylcholanthrene.
Male Sprague Dawley rats were injected intraperitoneally with 2-methoxy-4-amino-azobenzene (2-MeO-AAB) or 3-methylcholanthrene (MC), and then the expression of microsomal cytochrome P-450 isozymes in liver and extrahepatic tissues was investigated by means of immunological methods and a bacterial mutation test. The results of protein A-enzyme-linked immunosorbent assaying and immunoblotting using anti-rat cytochrome P-448 monoclonal antibodies showed that MC induced at least two microsomal cytochrome P-448 isozymes, a high spin form (cytochrome P-448H) and a low spin form (cytochrome P-448L), in liver, but that it induced only cytochrome P-448L in extrahepatic tissues such as lung, kidney, small intestine, and colon. The results also indicated that, in contrast to MC, 2-MeO-AAB selectively induced microsomal cytochrome P-448H in liver but did not induce any cytochrome P-448 isozymes in extrahepatic tissues. The activities of 9,000 X g supernatants from the individual organs, as to the mutagenic conversion of 3 aromatic amines (3-amino-1-methyl-5H-pyrido(4,3-b)indole, 2-amino-6-methyldipyrido(1,2-a: 3',2'-d)-imidazole and 3-methoxy-4-aminoazobenzene), toward Salmonella typhimurium TA 98 bacteria were dependent upon the quantity and/or quality of the microsomal cytochrome P-448 isozymes in the organs.
Degawa
M
M
Department of Hygienic Chemistry, Tohoku University, Miyagi.
Yamada
H
H
Hishinuma
T
T
Masuko
T
T
Hashimoto
Y
Y
D000588:Amines / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal; D001391:Azo Compounds / Q000494:pharmacology*; D019388:Cytochrome P-450 CYP1A2; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003580:Cytochromes / Q000096:biosynthesis*; D004790:Enzyme Induction / Q000187:drug effects; D007158:Immunologic Techniques; D007274:Injections, Intraperitoneal; D007527:Isoenzymes / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology*; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D009154:Mutation; D009928:Organ Specificity; D051381:Rats; D011919:Rats, Inbred Strains; D014781:Viscera / Q000187:drug effects / Q000201:enzymology; D010128:p-Aminoazobenzene / Q000031:analogs & derivatives / Q000494:pharmacology*
D000588:Amines; D000911:Antibodies, Monoclonal; D001391:Azo Compounds; D003580:Cytochromes; D007527:Isoenzymes; C053767:2-methoxy-4-aminoazobenzene; D008748:Methylcholanthrene; D010128:p-Aminoazobenzene; D003577:Cytochrome P-450 Enzyme System; C017170:Cyp1a2 protein, rat; D019388:Cytochrome P-450 CYP1A2