Depression of the Hepatic Cytochrome P-450 Monooxygenase System by Treatment of Mice with the Antineoplastic Agent 5-Azacytidine1

Abstract

The effects of 5-azacytidine (5-AC) administration on the he patic cytochrome P-450 systems of mice were studied. A single i.p. dose of 5-AC (25 mg/kg) to male Swiss-Webster mice caused about a 50% depression of microsomal cytochromes P-450 and os and of ethylmorphine W-demethylase and ethoxycoumarin Odeethylase activities. Depression was greatest 24 h after treat ment; by 48 to 72 h, cytochromes and drug metabolism had returned to near control values. Reduced nicotinamide adenine dinucleotide phosphate-cytochrome c reductase activity was also depressed by 5-AC, whereas reduced nicotinamide adenine dinucleotide-cytochrome c reductase was not. Incubation of 5AC with microsomes produced no effect on drug metabolism. The prolongation of hexobarbital sleeping time by 5-AC showed that drug metabolism is also impaired by 5-AC in vivo. These studies may have important clinical implications when certain drugs are coadministered with 5-AC.

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Cite this paper

@inproceedings{Gooderham2006DepressionOT, title={Depression of the Hepatic Cytochrome P-450 Monooxygenase System by Treatment of Mice with the Antineoplastic Agent 5-Azacytidine1}, author={Nigel J. Gooderham and G. J. Mannering}, year={2006} }