Characterization of benzo[a]pyrene metabolites isolated from muscle, liver, and bile of a juvenile flatfish.

Juvenile English sole (Parophrys vetulus) were force fed [3H]benzo[a]pyrene (BaP) and, after 24 h, metabolites were isolated from bile, liver, and muscle. The metabolites were analyzed by t.l.c. and h.p.l.c., and further characterized by u.v., fluorescence, or m.s. analyses. The identities of BaP 7,8-dihydrodiol, BaP 9,10-dihydrodiol, 1-hydroxy BaP, 3-hydroxy BaP, and 9-hydroxy BaP were confirmed. The amounts of BaP 7,8-dihydrodiol plus its conjugates (sulfates and glucuronides) were greater than twice the amounts of BaP 9,10-dihydrodiol plus its conjugates in bile. Liver also contained twice as much BaP 7,8-dihydrodiol as BaP 9,10-dihydrodiol, demonstrating that English sole produced larger amounts of the 7,8-isomer. T.l.c. analysis showed the presence of an unknown metabolite X migrating between BaP 9,10- and 7,8-dihydrodiols. M.s. showed X to be a non-vicinal dihydroxy derivative of BaP. Spectral properties of X were similar to those reported for a dihydroxy derivative, presumably the 3,9-dihydroxy BaP, formed from either 3- or 9-hydroxy BaP in the presence of rat liver microsomes. Compared to the dihydrodiols, X was resistant to both glucuronidation and sulfation. The resistance to form water-soluble metabolites may be responsible for the deposition of relatively large amounts (0.11% of the administered dose) of X in muscle; liver contained a much smaller amount (0.01%) of X. Thus, English sole converted BaP into metabolites known to be toxic to mammals, and these metabolites were found in the liver and edible tissue of the fish.