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Modification of benzo(a)pyrene metabolism with microsomes by addition of uridine 5'-diphosphoglucuronic acid
Abstract:
The metabolism of benzo(a)pyrene (BaP) by rat liver microsomes was examined in the presence and absence of uridine 5'-diphosphoglucuronic acid (UDPGA). BaP metabolites were separated by high-pressure liquid chromatography. The normal chromatographic patterns of the metabolities were altered by the addition of UDPGA. At concentrations of UDPGA at which the elutions of dihydrodiol components were unchanged, phenol and quinone elution profiles were selectively decreased. The decreased activities of microsomal mixed-function oxidases by UDPGA were also observed with the use of the aryl hydrocarbon hydroxylase assay. The decrease may not be due to inhibition of those enzymes, but rather to formation of glucuronide conjugates with oxygenated BaP metabolites. These results suggest that glucuronidation may be important in the detoxification of BaP.