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- W2044001575 abstract "Mutagenicity of the hepatocarcinogen 3′-hydroxymethyl-N,N-dimethyl-4-amino-azobenzene (3′-CH2OH-DAB) and its N-demethylated compounds was examined. Rat-liver 9000 × g supernatant (S9) fraction was used together with Salmonella typhimurium TA98 or TA100 as a tester strain. The expression of mutagenicity of 3′-CH2OH-DAB, 3′-hydroxymethyl-N-methyl-4-aminoazobenzene (3′-CH2OHMAB) and 3′-hydroxymethyl-4-aminoazobenzene (3′-CH2OH-AB) required the presence of both microsomes and cytosol as sources of enzymes as well as NADPH as a cofactor. 3′-CH2OH-AB showed positive mutagenicity on both strains in the presence of liver S9 from untreated rats whereas 3′-CH2OH-DAB and 3′-CH2OH-MAB were negative. The treatment of rats with polychlorinated biphenyls (PCB) or 3-methylcholanthrene (3-MC) resulted in a marked increase in the ability of S9 to activate these three compounds, whereas phenobarbital (PB) induction was not effective, except for the activation of 3′-CH2OH-AB. The mutagenic activities of the three compounds in strain TA98 were considerably decreased by adding cytochrome c to the S9 mixture, but the activation reactions were insensitive to 1-(1-naphthyl)-2-thiourea (NTU) and methimazole, high-affinity flavin-containing mono-oxygenase (FMO) substrates. Metyrapone and 2-diethylaminoethyl-2,2-diphenylvalerate hydrochloride (SKF-525A, potent inhibitors of cytochrome P450, had no inhibitory effect on the activation of these compounds by S9 from PCB-treated rat livers. In contrast, 7,8-benzoflavone (BF), a specific inhibitor of cytochrome P448, decreased the activities of 3′-CH2OH-DAB and 3′-CH2OH-MAB by 88 and 78%, respectively, but the inhibition was negligible for 3′-CH2OH-AB." @default.
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- W2044001575 date "1983-10-01" @default.
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- W2044001575 title "Participation of cytochrome P450 in mutagenic activation of the carcinogen 3′-hydroxymethyl-N,N-dimethyl-4-aminoazobenzene and its N-demethylated compounds by rat liver" @default.
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- W2044001575 doi "https://doi.org/10.1016/0165-7992(83)90136-7" @default.
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