Insight into mechanism of formation of c8 adducts in carcinogenic reactions of arylnitrenium ions with purine nucleosides.

For the most important arylnitrenium ion-guanosine C8 adducts in the reactions involving arylamine-initiated carcinogenesis, a detailed mechanism of their formation still remains unclear. In this paper, we employ quantum chemistry methods to explore this issue. Our study indicates that formation of these C8 adducts proceeds directly by additions of arylnitrenium ions to C8 position of nucleoside bases in DNA. The good agreements of theoretical rate constants, pK(a) value, and NMR chemical shifts of C8 intermediate with experimental data support this theoretical finding. Excitingly, predictions of what adducts can be observed in reactions of arylnitrenium ions with guanine and hypoxanthine are in fair agreement with experimental observations. This study answers an important question, in carcinogenesis researches, of what is the mechanism for formation of C8 adducts.