The stimulation of hydroxylation by carcinogenic and non-carcinogenic compounds

Abstract

Pretreatment of young rats and mice with certain drugs and polycyclic hydrocarbons stimulates the hydroxylation of biphenyl by liver microsomal preparations. Phenobarbitone, nikethamide and meprobamate, all increase the 4-hydroxylation of biphenyl but have little effect on the 2-hydroxylation. In contrast, the carcinogenic polycyclic hydrocarbons, 3,4-benzpyrene, 20-methylcholanthrene, and 1, 2, 5, 6-dibenzanthracene preferentially stimulate the 2-hydroxylation of biphenyl. Non-carcinogenic polycyclic hydrocarbons such as 1, 2, 6, 7-dibenzpyrene and 2, 3, 6, 7-dibenzanthracene stimulate neither mode of hydroxylation. Biphenyl is metabolized in vivo into 4-hydroxybiphenyl (20 per cent of the dose in rats, 25 per cent in mice) and 2-hydroxybiphenyl (2 per cent in rats, 5.5 per cent in mice). Pretreatment with phenobarbitone produces moderate stimulation of the 4-hydroxylation in rats, but not mice: 2-hydroxylation is unaffected. Pretreatment with benzpyrene produces stimulation of 2-hydroxylation in both species, but does not affect the 4-hydroxylation. It is suggested that a correlation may exist between the carcinogenicity of polycyclic hydrocarbons and their induction of the hepatic microsomal enzyme responsible for the 2-hydroxylation of biphenyl.