CADMIUM INHIBITS BPDE ALKYLATION OF DNA IN THE MAJOR GROOVE BUT NOT IN THE MINOR-GROOVE

Cadmium, a constituent of tobacco, has the potential to act in synergy with other carcinogens in tobacco smoke. Working on the hypothesis th at cadmium interactions with DNA enhances the mutagenic lesions induce d by tobacco carcinogens, we investigated the site and sequence select ivity of DNA binding by cadmium using DNA reactive chemical probes. Ou r results show that this divalent cation binds to N-7 guanines with a great preference for those occurring in runs of G's. Further, cadmium considerably diminishes N-7 guanine alkylation by the tobacco carcinog en metabolite BPDE; however, the biologically relevant guanine alkylat ion in the minor groove by BPDE was not affected. The relevance of our findings to cadmium's role in the tobacco carcinogenesis is discussed . (C) 1998 Academic Press.