Patterns of benzo[a]pyrene metabolism by varied species, organs, and developmental stages of fish

Microsomal preparations of liver from adults of several (teleost) fish species, including scup (Stenotomus chrysops), winter flounder (Pseudopleuronectes americanus), and killifish (Fundulus heteroclitus), metabolized the model polycyclic hydrocarbon carcinogen benzo[a]pyrene (BP) with a marked regiospecificity, forming high percentages of benzo-ring derivatives, but particularly BP-7,8-dihydrodiol and BP-9,10-dihydrodiol. The identity of these products was established by mass spectrometry of metabolites formed by scup (S. chrysops) liver microsomes compared with the spectra obtained for authentic trans-dihydrodiols. Whereas the benzo-ring dihydrodiols equaled 40-60% of the total ethyl acetate-soluble metabolites formed by liver microsomes of the various species, the K-region metabolite BP-4,5-dihydrodiol was formed in small or undetectable amounts. Microsomal preparations of kidney and gill from S. chrysops formed BP-7,8-dihydrodiol and BP-9,10-dihydrodiol in proportions like those seen with liver of the same species. Embryonic tissues of F. heteroclitus metabolized BP with a regiospecificity similar to that exhibited by adult liver microsomes. Isomeric forms of BP-7,8-dihydrodiol are potent proximate carcinogens, and activation of BP to mutagenic and carcinogenic derivatives is associated with metabolism on the benzo ring of BP. The widespread appearance of regiospecificity for this portion of the BP molecule may be reflected in structural requirements for metabolism of other hydrocarbons and indicate that fish are useful in the study of various factors that affect tumorigenesis by polycyclic hydrocarbons.