Alkylation products of DNA bases by simple epoxides

The reaction products of a series of epoxides with deoxyribonucleosides were characterized using ultraviolet, and NMR spectroscopy. The epoxides included structural analogues which are known to differ extensively in their mutagenic potency: propylene oxide, glycidol, epichlorohydrin, trichloropropylene oxide and styrene oxide. Trichloropropylene oxide, epichlorohydrin and glycidol reacted with deoxyguanosine producing a major adduct of 1,7-(or 1,9-)dialkylguanine. All of the epoxides produced a 7-alkylguanine adduct, with the possible exception of styrene oxide. Propylene oxide, glycidol and epichlorohydrin reacted with deoxyadenosine at N-6. Glycidol, trichloropropylene oxide and styrene oxide reacted with deoxycytidine at N-3. It was concluded that the structurally related epoxides tend to react largely in a uniform way with nucleic acid bases. Thus, the reaction rates rather than the major adducts explain the differential mutagenicity of the epoxides.