MOLECULAR ORIGIN OF CANCER ESTROGENS AS ENDOGENOUS CARCINOGENS FOR BREAST CANCER

自1987年以来，我们已经检查了100多个DNA碱基和核苷 含有致癌的多环芳烃 （PAH）。 最近，我们扩大了研究范围， 可能致癌的类固醇激素（例如，雌激素）。 这些 材料与PAH具有相同的化学性质;即 材料引起DNA的修饰和脱嘌呤。 我们现在 使用低能量碰撞激活（在三重四极杆上），以及 MALDI/飞行时间仪器上的源后分解（PSD） 以及高能碰撞活化作为可能的方法， 从修饰过的DNA中提取结构信息 目标是 开发和利用质谱分析方法来分析组织， 生物流体样品用于支持该机制的生物标志物 研究致癌作用，并确定有患乳腺癌风险的妇女。 质量 光谱法已经被用来表明这些儿茶酚 雌激素修饰DNA和谷胱甘肽。 更重要的是，现在 用于检测暴露于以下物质的仓鼠的组织和尿液中的生物标志物： 雌激素醌类。

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.