ESTROGENS AS ENDOGENOUS CARCINOGENS FOR BREAST CANCER

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. 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. The goal is to develop and utilize HPLC electrospray 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. Moreover, it is now being used to detect biomarkers in tissue and urine of hamsters and in cancer-cell cultures exposed to estrogens and estrogen quinones. To increase the specificity of the method, we are incorporating accurate mass detection of the various biomarkers.