Stereoselective metabolism of 8- and 9-fluorobenzo[a]pyrene by rat liver microsomes: absolute configurations of trans-dihydrodiol metabolites.

Rat liver microsomal metabolism of 8-fluorobenzo[a]pyrene (8-fluoro-BaP) generated 3-hydroxy-8-fluoro-BaP, 8-fluoro-BaP trans-4,5-dihydrodiol, and 8-fluoro-BaP, 3,6-quinone as major products. A minor metabolite of 8-fluoro-BaP was tentatively assigned as 8-fluoro-BaP 9,10-dihydrodiol. Metabolism of 9-fluorobenzo[a]pyrene (9-fluoro-BaP) gave 3-hydroxy-9-fluoro-BaP, 9-fluoro-BaP trans-4,5-dihydrodiol, 9-fluoro-BaP trans-7,8-dihydrodiol, and 9-fluoro-BaP 3,6-quinone. All three dihydrodiol metabolites were optically active. Comparison of the circular dichroism spectra of BaP 4R,5R-dihydrodiol, 6-bromo-BaP 7R,8R-dihydrodiol, and 6-fluoro-BaP 7R,8R-dihydrodiol with those of the respective dihydrodiol metabolites allowed assignments of an R,R absolute configuration to the major enantiomers of the three dihydrodiol metabolites.