Age-and sex-related differences in rat liver microsomal enzymes and their inducibility by toluene.

Abstract

In the liver microsomes of toluene-treated and control Sprague-Dawley rats (n = 148, males and females aged 13-93 days), the contents of cytochrome P-450 and b5 and the activities of NADPH-cytochrome c reductase and four monooxygenases were studied. In male control rats, cytochrome contents and NADPH-cytochrome c reductase, aminopyrine N-demethylase and aniline hydroxylase activities increased to the age of one month, and after a slight decrease in cytochrome concentrations, the average adult level was reached by the age of two months. Aniline hydroxylase and 7-ethoxycoumarine O-deethylase activities decreased to about half at the same age period. In control female rats, the activities of aminopyrine N-demethylase and aniline hydroxylase decreased after the age of one month, and they remained at a considerably lower level in adult females than in males. The sex-dependence of other enzymes was negligible. Toluene induction was already well developed in the youngest age group of both sexes; in most cases the induced enzyme levels in young rats were as high or higher than in adults. In adult female rats, toluene induction of all enzymes was weaker than in males. In male rats, the toluene-induced level of aniline hydroxylase and 7-ethoxycoumarine O-deethylase showed deep minima at the age of 43-53 days, at the puberty of rats.