The rate of oxidative demethylation of aminopyrine by preparations of microsomes from male rat livers decreased following whole-body irradiation, reaching a minimum, of 25% of the control value, on the 4th and 5th days after 850 rads. Oxidative demethylation in preparations of microsomes from female rats or male or female mice was unaffected by this dose of irradiation. The decreased rate in male rats was caused mainly by an increase of the Km for the reaction from 0.52 to 1.60 mM. The rate of hydroxylation of biphenyl in the male rat liver was also depressed by whole-body irradiation to a similar extent as oxidative demethylation. Cytochrome P450 concentration in the microsomes was unaffected by irradiation, but NADPH cytochrome c reductase activity was depressed. Synthesis and the output of corticosteroids from the adrenal was unaffected by 850 rads whole-body irradiation. Nearly maximum activity of the oxidative demethylation system, as measured by Km, was restored by the injection of testosterone into male rats, and it is therefore considered that a reduced output of this hormone, possibly resulting from reduced anterior pituitary activity, is a primary cause of inhibition of oxidative demethylation and hydroxylation which follows whole-body irradiation.

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