ESTROGENS AS ENDOGENOUS CARCINOGENS FOR BREAST CANCER

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。自1987年以来，我们已经检测了100多个DNA碱基和核苷，这些DNA碱基和核苷被致癌性多环芳烃（PAH）修饰。最近，我们扩大了研究范围，包括潜在致癌的类固醇激素（如雌激素）。这些材料与多环芳烃具有相同的化学性质；即物质会引起DNA的修饰和去嘌呤化。目标是开发和利用高效液相色谱电喷雾质谱分析方法来分析组织和生物液体样本中的生物标志物，以支持这种致癌机制，并确定有乳腺癌风险的妇女。质谱法已经被用来证明这些儿茶酚类雌激素可以修饰DNA和谷胱甘肽。此外，它现在被用于检测仓鼠组织和尿液中的生物标志物，以及暴露于雌激素和雌激素醌的癌细胞培养物。为了提高该方法的特异性，我们结合了各种生物标志物的准确质量检测。

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.