Genetic differences in the induction of aryl hydrocarbon hydroxylase and its components by 3-methylcholanthrene in liver and lung microsomes among four strains of guinea pigs

Abstract

Four strains of guinea pigs (Hartley, No. 2, No. 13 and JY-1) were examined for the effects of intraperitoneal treatment with 3-methylcholanthrene on aryl hydrocarbon hydroxylase activity, total cytochrome P-450 content in liver and lung microsomes, and NADPH-cytochrome c reductase activity in liver microsomes. Following treatment with 3-methylcholanthrene at a dose of 50 mg/kg body weight, aryl hydrocarbon hydroxylase activity and cytochrome P-450 content in liver were both increased in all the strains used, and the activity of NADPH-cytochrome c reductase in liver was also increased in all strains except No. 13. While the cytochrome P-450 content in lung was increased in all the strains except No. 13, there was no increase in the aryl hydrocarbon hydroxylase activity in lung from any strain of guinea pig examined. When the dose of 3-methylcholanthrene was increased to 250 mg/kg body weight, an apparent induction of aryl hydrocarbon hydroxylase was detected in the lung from the Hartley strain of guinea pigs, but not in the other three strains. In summary, marked differences were seen in sensitivity to 3-methylcholanthrene between liver and lung, and apparent strain differences were observed among the guinea pigs used in this experiment.