Effects of Harman and Norharman on the Metabolism of Aniline and p-Dimethylaminoazobenzene

Abstract

The effects of harman (l-methyl-9H-pyrido[3, 4-b]indole) and norharman (9H-pyrido[3, 4-b]indole) on the metabolism and mutagenicity of aniline and p-dimethylaminoazobenzene and on the metabolic enzymes in the liver microsomes of rats were investigated in vitro. The following results were obtained.1) The metabolism of aniline to p-aminophenol was greatly inhibited when harman or norharman was added to liver microsomes. The effects of norharman were greater than those of harman.2) p-Dimethylaminoazobenzene metabolized to aniline without accumulations of p-methylaminoazobenzene and p-aminoazobenzene when neither harman nor norharman was added to microsomes.3) The metabolism of p-dimethylaminoazobenzene to aniline was slightly inhibited, and there were accumulations of p-dimethylaminoazobenzene, p-methylaminoazobenzene and p-aminoazobenzene, when norharman was added to microsomes.4) The mutagenic activities of o-, m-, p-aminophenol and nitrosobenzene, the metabolites of aniline, were tested for Salmonella typhimurium TA98. It was found that nitrosobenzene was mutagenic only when norharman was added with S-9 Mix to the incubation mixture.5) The mutagenic activities of p-dimethylaminoazobenzene, p-phenylenediamine, p-aminophenol and aniline, the metabolites of p-dimethylaminoazobenzene, were tested for Salmonella typhimurium TA98. It was found that p-methylaminoazobenzene, p-aminoazobenzene and aniline were mutagenic only when norharman was added with S-9 Mix to the mixture.6) The levels of inhibition by harman and norharman on the enzymatic activity of aniline hydroxylase were high, but on those of aminopyrine demethylase were low. Norharman inhibited the enzymatic activity of aryl hydrocarbon hydroxylase, but harman did not.