Chemical linkage of carcinogenic 3,4-benzpyrene to DNA in aqueous solution induced by peroxide and iodine.

Abstract

THE origin of the biological specificity of polycyclic hydrocarbons has long confronted investigators interested in carcinogenesis. The affinity and the extent of physical binding of carcinogenic and non-carcinogenic polycyclic hydrocarbons (for example, 3,4-benzpyrene against 1,2-benzpyrene or 1,2,5,6-dibenzanthracene against 1,2,3,4-dibenzanthracene) to DNA cannot be correlated with carcinogenicity1. Chemical complexes of polycyclic carcinogens with DNA have been found in biological systems2,3, and the available data indicate that the extent of complex formation may be correlated with the carcinogenic potency of these compounds3. Ts'o and Lu4 have reported the formation of a covalent linkage between 3,4-benzpyrene (3,4-BP) and DNA in aqueous solution, induced by photoirradiation. Preliminary experiments with carcinogenic and non-carcinogenic hydrocarbons have shown no selective activation of carcinogenic compounds by photoirradiation. Rapaport and Ts'o5 have achieved a covalent linkage between 3,4-BP and DNA by X-irradiation which suggests that polycyclic hydrocarbons may be activated by hydroxyl radicals. Rochlitz6 reported that a covalent linkage between 3,4-BP and pyridine had been induced by iodine vapour in a pyridine–solid phase system. Here we wish to report the formation of a 3,4-BP–DNA covalent linkage in an aqueous, neutral solution, at 0°–50° C, induced by peroxide and iodine. Little or no 1,2-BP–DNA chemical complex formation was found in identical conditions. Thus the chemical reactivity of this pair of isomers with DNA in the present aqueous system can be correlated with their carcinogenicity.