MOLECULAR ORIGIN OF CANCER ESTROGENS AS ENDOGENOUS CARCINOGENS FOR BREAST CANCER

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Since 1987, we have examined over 100 DNA bases and nucleosides that are modified with carcinogenic polycyclic aromatic hydrocarbons (PAH). More recently, we have expanded the research to include potentially carcinogenic steroid hormones (e.g., estrogens). These materials share a chemical property with that of PAH; that is both materials cause modification and depurination of DNA. We are now using low energy collisional activation (on triple quadrupoles), and post-source decompositions (PSD) on MALDI/time-of-flight instruments as well as high-energy collisional activation as possible methods for extracting structural information from modified DNA. The goal is to develop and utilize mass spectrometry methods to analyze tissue and biological fluid samples for biomarkers that support this mechanism for carcinogenesis and identify women at risk for breast cancer. Mass spectrometry has already been used to show that these catechol estrogens modify DNA and glutathione . M oreover, it is now being used to detect biomarkers in tissue and urine of hamsters exposed to estrogen quinones.