Genetic evidence for many unique liver microsomal P-450-mediated monooxygenase activities in heterogeneic stock mice.

Abstract

Total cytochrome P-450 content, the Soret maximum of the reduced P-450 CO complex, NADPH-cytochrome c reductase activity, and 20 monooxygenase activities were determined in liver microsomes from each of 12 individual Heterogeneic Stock (HS) mice a t varying times after 3-methylcholanthrene treatment.The choice of genetically very heterogeneous mice and the possibility of different turnover rates (synthesis/degradation) during the 3-methylcholanthrene induction process provided us with a strong likelihood of detecting differences in drug-metabolizing enzyme activities.Such diversity would also be expected among the human population.The substrates included benzo[u]pyrene, ethoxyresorufin, biphenyl, p-nitroanisole, 2-acetylaminofluorene, 7-ethoxycoumari11, zoxazolamine, estradiol-l7B, testosterone, progesterone, pregnenolone, dehydroepiandrosterone, and aldrin.By two-factor analysis of variance, 18 unique liver microsomal monooxygenase activities appear to be distinctly different from one another, out of the 20 activities chosen for study.Ethoxyresorufin 0-deethylase activity is significantly corre-' The abbreviation used is: HS mice, heterogeneic stock mice.