Mori Y, Niwa T, Toyoshi K
Carcinogenesis. 1983 Nov;4(11):1487-9. doi: 10.1093/carcin/4.11.1487.
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.
利用特异性抗体和抑制剂,在沙门氏菌检测系统中研究了两种细胞色素P-450(苯巴比妥处理大鼠肝微粒体的主要细胞色素P-450成分(PB-P-450)和3-甲基胆蒽处理大鼠的细胞色素P-450(MC-P-448))对3'-甲基-N,N-二甲基-4-氨基偶氮苯(3'-Me-DAB)及其八种代谢产物的诱变活化作用。抗MC-P-448抗体在菌株TA98中显著抑制了3'-Me-DAB、3'-CH2OH-DAB、它们的三种N-去甲基化化合物、3'-CHO-DAB和3'-Me-4'-OH-DAB的诱变性,而抗PB-P-450抗体对它们诱变性的抑制作用小于29%。相反,抗MC-P-448抗体对3'-羟甲基-N-甲基-4-氨基偶氮苯(3'-CH2OH-MAB)和3'-COOH-DAB的诱变性没有抑制作用或仅有轻微抑制(29%)。然而,与其他七种氨基偶氮染料一样,这两种化合物的诱变性都被7,8-苯并黄酮显著抑制。这些结果表明,大鼠肝细胞色素P-450,尤其是MC-P-448,参与了氨基偶氮染料的诱变活化。文中还讨论了第二种形式的细胞色素P-448在3'-CH2OH-MAB和3'-COOH-DAB诱变活化中的作用。