MOLECULAR ORIGIN OF CANCER ESTROGENS AS ENDOGENOUS CARCINOGENS FOR BREAST CANCER

自1987年以来，我们检测了100多个dna碱基和核苷。 用致癌的多环芳烃进行修饰 (PAH)。最近，我们扩大了研究范围，包括 可能致癌的类固醇激素(如雌激素)。这些 材料与多环芳烃有一个共同的化学性质，即两者 材料会引起DNA的修饰和脱氨。我们现在是 使用低能量碰撞激活(在三个四极上)，以及 MALDI/飞行时间仪器的震源后分解(PSD) 以及高能碰撞激活作为可能的方法 从修饰的DNA中提取结构信息。我们的目标是 开发和利用质谱学方法来分析组织和 支持这一机制的生物标志物的生物流体样本 用于癌症发生，并确定乳腺癌风险的女性。质量 光谱已经被用来表明这些邻苯二酚 雌激素可以修饰DNA和谷胱甘肽。更重要的是，它现在是 用于检测暴露于地鼠体内的组织和尿液中的生物标志物 雌激素醌类化合物。

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.