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 that cadmium interactions with DNA enhances the mutagenic lesions induced by tobacco carcinogens, we investigated the site and sequence selectivity of DNA binding by cadmium using DNA reactive chemical probes. Our results show that this divalent cation binds to N7 guanines with a great preference for those occurring in runs of G's. Further, cadmium considerably diminishes N7 guanine alkylation by the tobacco carcinogen metabolite BPDE; however, the biologically relevant guanine alkylation in the minor groove by BPDE was not affected. The relevance of our findings to cadmium's role in the tobacco carcinogenesis is discussed.
Prakash
A S
AS
National Research Centre for Environmental Toxicology, Queensland, Australia.
Rao
K S
KS
Dameron
C T
CT
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000378:metabolism*; D000478:Alkylation / Q000187:drug effects; D000818:Animals; D001345:Autoradiography; D001665:Binding Sites; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D002417:Cattle; D004247:DNA / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D018983:DNA Footprinting; D009607:Nitrosourea Compounds / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000378:metabolism; D013050:Spectrometry, Fluorescence
D009607:Nitrosourea Compounds; D009943:Organophosphorus Compounds; D002104:Cadmium; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide; D004247:DNA; C054368:fotemustine