Drug metabolism and drug-induced spectral interactions in human fetal liver microsomes

Abstract

Properties of a mono-oxygenase system in human fetal liver microsomes were studied. The levels of cytochrome P-450 and NADPH-cytochrome c reductase were 20 and 30 per cent, respectively of rat liver microsomal levels. Corresponding percentages for homogenates were 13 and 18 per cent, respectively. Hepatic 12,000 g supernatants from human fetuses were found to catalyze the hydroxylation of 3,4-benzpyrene and aniline and the N-demethylation of aminopyrine. These activities were 2, 12 and 11 per cent of those in adult rat liver. The cytochrome P-450- and NADPH-cytochrome c reductase-related turn-over-numbers for aminopyrine and aniline were of the same order of magnitude in human fetal and adult livers and in rat liver. The fetal turn-over-number for 3,4-benzpyrene was small compared with adult and rat values. Spectral changes induced by the addition of various compounds to liver microsomes were studied. Aminopyrine and hexobarbital were found to yield type I spectral changes with rat or adult human microsomes, but with fetal microsomes these compounds yielded a type II spectral change except in some cases when hexobarbital in low concentration yielded a type I change. Aniline and n-octylamine induced type II spectral changes with both adult and fetal microsomes. The relative magnitudes of spectral changes differed greatly between fetal and adult microsomes.