Effects of superoxide generated in vitro on glucuronidation of benzo[a]pyrene metabolites by mouse liver microsomes.
Glucuronidation of benzo[a]pyrene (B[a]P) metabolites, generated in situ by oxidative pathways, was studied using mouse liver uninduced microsomes. No coupling was evident between UDP-glucuronyltransferase and oxygenation of B[a]P. UDPGA protected microsomal macromolecules against binding of reactive B[a]P metabolites. Superoxide, and other reactive oxygen species decreased both the overall B[a]P metabolism and glucuronidation of some B[a]P metabolic products, and caused more extensive binding to macromolecules; UDPGA was less protective in this condition. Peroxidation of microsomes differentially affected glucuronidation of various metabolites of B[a]P, and of various model substrates, indicating that multiple glucuronyltransferases are involved in the conjugation of hydroxylated metabolites of B[a]P.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D005260:Female; D014453:Glucuronosyltransferase / Q000378:metabolism*; D008054:Lipid Peroxides / Q000378:metabolism; D051379:Mice; D008811:Mice, Inbred DBA; D008862:Microsomes, Liver / Q000187:drug effects / Q000201:enzymology*; D013481:Superoxides / Q000378:metabolism*; D014535:Uridine Diphosphate Glucuronic Acid / Q000494:pharmacology
D008054:Lipid Peroxides; D013481:Superoxides; D014535:Uridine Diphosphate Glucuronic Acid; D001564:Benzo(a)pyrene; D014453:Glucuronosyltransferase