Effects of inducers on the regio- and stereoselective metabolism of benzo[a]pyrene by mouse tissue microsomes.
The metabolism of benzo[a]pyrene (BP) by microsomal fractions of the skin, lungs and liver of the mouse, and the effects on this process of pretreatment with the xenobiotics phenobarbital (PB) and 3-methylcholanthrene (3-MC) were examined. Differences between the untreated tissues were found both in terms of the total amounts of diol recovered and in the relative proportions of the individual diols extracted following incubation. Induction with PB or 3-MC significantly altered the profiles of metabolic diols obtained with epidermal and hepatic microsomes compared with their respective controls. Pulmonary microsomes showed similar trends to those obtained with liver microsomes but these were not statistically significant. The optical purity of the BP-7,8-diol that was formed by each microsomal type was examined by direct resolution of the enantiomers on HPLC using a chiral stationary phase. In each case the (-)-7R,8R-enantiomer predominated. Pretreatment with 3-MC significantly decreased the optical purity of BP-7,8-diol recovered from incubations with skin microsomes, but significantly increased the optical purity of the diol extracted from incubations with lung and liver microsomes. In addition to the diols, an unidentified BP metabolite was found that eluted between BP-9,10- and 4,5-diol on a reverse-phase high-performance liquid chromatography (HPLC) system and which represented a major product in extracts of incubations of BP with both induced and uninduced skin and lung microsomal fractions.
D000818:Animals; D001564:Benzo(a)pyrene / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D004101:Dihydroxydihydrobenzopyrenes / Q000378:metabolism*; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D010634:Phenobarbital / Q000633:toxicity; D012867:Skin / Q000187:drug effects / Q000378:metabolism*
D004101:Dihydroxydihydrobenzopyrenes; D001564:Benzo(a)pyrene; D008748:Methylcholanthrene; D010634:Phenobarbital