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.