Immunochemical study on the contributions of two molecular species of cytochrome P-450 in mutagenesis by selected aminoazo dyes.
The relative contributions of two species of cytochrome P-450, the major cytochrome P-450 components of liver microsomes of phenobarbital-treated rats (PB-P-450) and of 3-methylcholanthrene-treated rats (MC-P-448), in the mutagenic activation of 3'-methyl-N,N-dimethyl-4-aminoazobenzene (3'-Me-DAB) and its eight metabolites were studied in the Salmonella assay system using specific antibodies and inhibitors. The antibody against MC-P-448 considerably inhibited the mutagenicities of 3'-Me-DAB, 3'-CH2OH-DAB, their three N-demethylated compounds, 3'-CHO-DAB, and 3'-Me-4'-OH-DAB in strain TA98, whereas the antibody against PB-P-450 inhibited their mutagenicities less than 29%. In contrast, the antibody against MC-P-448 caused no or slight (29%) inhibition of the mutagenicities of 3'-hydoxymethyl-N-methyl-4-aminoazobenzene (3'-CH2OH-MAB) and 3'-COOH-DAB. However, the mutagenicities of both compounds were considerably inhibited by 7,8-benzoflavone, like those of other seven aminoazo dyes. These results demonstrate that rat liver cytochrome P-450, especially MC-P-448, is involved in mutagenic activation of the aminoazo dyes. Participation of a second form of cytochrome P-448 in mutagenic activation of 3'-CH2OH-MAB and 3'-COOH-DAB is discussed.
D000818:Animals; D001711:Biotransformation; D004396:Coloring Agents / Q000633:toxicity*; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D008749:Methyldimethylaminoazobenzene / Q000378:metabolism / Q000633:toxicity*; D008862:Microsomes, Liver / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009153:Mutagens; D009154:Mutation; D051381:Rats; D011919:Rats, Inbred Strains; D012486:Salmonella typhimurium / Q000187:drug effects; D004124:p-Dimethylaminoazobenzene / Q000031:analogs & derivatives*
D004396:Coloring Agents; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; D009153:Mutagens; D008749:Methyldimethylaminoazobenzene; D003577:Cytochrome P-450 Enzyme System; D004124:p-Dimethylaminoazobenzene