Depression of the hepatic cytochrome P-450 monooxygenase system by treatment of mice with the antineoplastic agent 5-azacytidine.
The effects of 5-azacytidine (5-AC) administration on the hepatic 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 b5 and of ethylmorphine N-demethylase and ethoxycoumarin O-deethylase activities. Depression was greatest 24 h after treatment; 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 5-AC 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.
Gooderham
N J
NJ
Mannering
G J
GJ
D000818:Animals; D001374:Azacitidine / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D003577:Cytochrome P-450 Enzyme System; D003573:Cytochrome b Group / Q000037:antagonists & inhibitors; D015786:Cytochromes b5; D004579:Electron Transport / Q000187:drug effects; D005037:Ethylmorphine-N-Demethylase / Q000037:antagonists & inhibitors; D006591:Hexobarbital / Q000494:pharmacology; D066298:In Vitro Techniques; D007372:Interferons / Q000096:biosynthesis; D008099:Liver / Q000201:enzymology*; D008297:Male; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D051381:Rats; D011919:Rats, Inbred Strains; D012890:Sleep / Q000187:drug effects
D003573:Cytochrome b Group; D007372:Interferons; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006591:Hexobarbital; D010105:Oxygenases; D005037:Ethylmorphine-N-Demethylase; D001374:Azacitidine