Non-B DNA structure: preferential target for the chemical carcinogen glycidaldehyde

The effect of DNA conformation on the reaction specificities of the chemical carcinogen glycidaldehyde (GDA) was examined. Supercoiled plasma DNA harboring a poly(dG)-poly(dC) tract, which folds sharply into halves from the center of the tract to form a tetra-stranded structure containing either a dG.dG.dC triplex structure in the presence of Mg2+ or a dC+.dC.dC triplex structure in the absence of Mg2+ was chosen as the reaction substrate. The reactive sites alkylated by GDA were determined at a single base resolution after these sites were specifically cleaved with a combination of either the hydrazine and piperidine or formic acid and piperidine reactions. The results show that at pH 5-7, GDA reacts preferentially with DNA bases that are involved in the altered DNA conformations. Interestingly, in addition to the known reaction of GDA with guanine residues, it was also found to be highly reactive with specific cytosine residues that reside in the altered DNA conformations. These GDA-reactive cytosine residues were unpaired as judged by their reactivity with the unpaired DNA base specific probe, chloroacetaldehyde. Therefore, it appears that DNA conformation plays a major role in determining the reaction specificities of GDA.