Several carcinogens are bound covalently to cellular nucleic acids. This is also the case with polycyclic hydrocarbon carcinogens, but their precise mechanism of in vivo activation to reactive forms and the structure(s) of the nucleic acid adducts are not known. This study demonstrates that in the presence of rat liver microsomes and reduced nicotinamide adenine dinucleotide phosphate there is covalent attachment of tritiated benzo(α)pyrene (BP) to transfer RNA, DNA, certain synthetic polyribonucleotides, and an RNA species endogenous to the microsomal fraction. Evidence has been obtained that the binding occurs mainly to guanine and, to a lesser extent, adenine residues and is not simply an artifact of tritium exchange. The microsomal-mediated binding of [3H]BP to nucleic acids requires reduced nicotinamide adenine dinucleotide phosphate and is inhibited by 7,8-benzoflavone, glutathione, and magnesium. It is enhanced somewhat by the addition of styrene oxide, cyclohexene oxide, and trichloropropylene oxide. These results provide the first evidence that: (a) the microsome-mediated binding of [3H]BP to nucleic acids is not just due to tritium exchange; (b) a derivative of the hydrocarbon is covalently bound to the nucleic acid, and not simply intercalated; (c) there is a preferential binding to guanine residues; and (d) in addition to binding to exogenous nucleic acids, [3H]BP is bound to an RNA species present in the microsomes. Our data are consistent with but do not prove that nucleic acid binding of this polycyclic hydrocarbon proceeds via an epoxide intermediate.


This research was supported by National Cancer Institute Grant CA 02332.

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