Effects of inhibition of NADPH: cytochrome P-450 reductase on benzo(a)pyrene metabolism in mouse liver microsomes.
1. Effects of antioxidants (butylated hydroxytoluene and nor-dihydroguaiaretic acid), vitamin K-related quinones (vitamin K1 and coenzyme Q10) and inorganic copper (CuSO4), in concentrations inhibiting NADPH: cytochrome P-450 reductase, were re-examined on benzo(a)pyrene metabolism in mouse liver uninduced microsomes. 2. It was found that all these compounds decrease production of the two-electron oxygenation products of benzo(a)pyrene (monophenoles, diols) and the amounts of glucuronides in a manner parallel to their inhibitory potency against NADPH: cytochrome P-450 reductase. 3. No correlation was found between amounts of one-electron oxidation products of benzo(a)pyrene and inhibition of NADPH: cytochrome P-450 reductase. 4. Without added UDPGA the compounds studied decreased protein associated benzo(a)pyrene metabolites in parallel to the decreased overall metabolism of this polyaromatic hydrocarbon. 5. The mode of action of the studied compounds is discussed.
Byczkowski
J Z
JZ
Grace Cancer Drug Center, Roswell Park Memorial Institute, New York State Department of Health, Buffalo 14263.
Gessner
T
T
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000378:metabolism*; D003067:Coenzymes; D003300:Copper / Q000494:pharmacology; D019327:Copper Sulfate; D005260:Female; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D009251:NADPH-Ferrihemoprotein Reductase / Q000037:antagonists & inhibitors*; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000494:pharmacology; D014535:Uridine Diphosphate Glucuronic Acid / Q000494:pharmacology; D010837:Vitamin K 1 / Q000494:pharmacology
D000975:Antioxidants; D003067:Coenzymes; D014451:Ubiquinone; D014535:Uridine Diphosphate Glucuronic Acid; D001564:Benzo(a)pyrene; D003300:Copper; D010837:Vitamin K 1; D009251:NADPH-Ferrihemoprotein Reductase; C024989:coenzyme Q10; D019327:Copper Sulfate