My research centers around elucidating mechanisms of activation of carcinogens, identifying carcinogen-DNA adducts, and correlating adducts with oncogenic mutations. From our previous study of polycyclic aromatic hydrocarbon (PAH) metabolism and DNA adducts, we have demonstrated that the predominant adducts are lost by depurination, leaving mutagenic apurinic sites in the DNA. This research involved identification and quantitation of PAH-DNA adducts and correlation of the adducts with Harvey-ras mutations in mouse skin papillomas induced by the PAH. We have extended our studies to endogenous catechol estrogen metabolites and found that the carcinogenic metabolites form depurinating N3Ade and N7Gua adducts in DNA. We hypothesize that this is the pathway of initiation for human breast, ovarian, thyroid, prostate and other cancers. Studies in test tubes, laboratory animal models, cell culture models and human subjects have demonstrated the validity of this hypothesis. Now we are working on the early detection of cancer risk and prevention of cancer by selected natural compounds.
