Voltammetric studies of damages in DNA by mutagenic and carcinogenic alkylating chemicals

Voltammetry provides new insights into the effects exerted in vitro by methylation of native DNA. Applying single sweep voltammetry at a stationary mercury electrode the successive steps of the destabilization of alkylated DNA are investigated. The methylation of the nucleic acids is manifested by a specific electrochemical response, due to the 7‐methylguanine, a major product of the methylation of DNA. Short time effects of the methylation include the labilization of 4 to 5 base pairs per methylated guanine base. Furthermore, uncommon protonation properties of the base 7‐methylguanine‐cytosine have been detected. Long term effects of the methylation are ultimately spontaneous hydrolytic strand breaks induced by the prior depurination connected with the release of the 7‐methylguanine from the methylated DNA. A half time t_1/2 of 102 h for the depurination at 37°C has been determined. The depurination and the subsequent strand breaks alter the hydrodynamic properties of the damaged DNA, an effect which can be sensitively followed with voltammetry via the resulting changes in the diffusion coefficient of the damaged biopolymer.