The preparation of some specifically tritium labelled carcinogenic hydrocarbons and their covalent binding to DNA

Abstract

Syntheses are described for the preparation of [9(10)-³H]anthracene, [6-³H]benzo[a]pyrene, and [7-Me-³H₁]-7,12-dimethylbenz[a]anthracen. The nature and extent of covalent binding of these hydrocarbons to calf thymus DNA resulting from ultraviolet or gamma irradiation, from oxidative processes involving iodine or hydrogen peroxide, or from oxygen in conjunction with NADPH and a rat liver microsomal preparation is investigated. The displacement of tritium on hydrocarbon bonding to DNA identifies position-6 in benzo[a]pyrene and position-9 in anthracene as sites for DNA binding by irradiation processes or by chemical oxidation. Metabolic binding of benzo[a]pyrene to DNA shows an altered regioselectivity while that for 7,12-dimethylbenz[a]anthracene appears to to involve the 7-methyl group.