EPIGENIC TOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 多环芳烃(PAHs)是烟草烟雾中的丰富成分，与癌症的形成有关。大量研究表明，这些化合物会导致基因损伤，从而导致癌症。然而，癌症不仅仅是不可逆转的诱变事件的后果，还涉及可逆的表观遗传事件。因此，有必要在表观遗传水平上重新评估多环芳烃的毒性。缝隙连接细胞间通讯(GJIC)主要调节表观遗传学改变基因表达的信号转导通路。有相当多的证据表明，GJIC的异常调节与肿瘤促进的非遗传毒性步骤有关。我们与厄普汉姆实验室合作，设计了一种蛋白质组学方法，以检测由于多环芳烃引起的蛋白质丰度的早期变化和翻译后修饰。

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. Polycyclic aromatic hydrocarbons (PAHs) are abundant components of tobacco smoke that have been implicated in cancer formation. A large body of work indicates that these compounds induce genetic damage and this results cancer. However, cancer is not solely the consequence of non-reversible mutagenic events but also involves reversible, epigenetic events. Thus, there is a need to reassess the toxicity of PAHs at the epigenetic level. Gap junctional intercellular communication (GJIC) centrally modulates signal transduction pathways that epigenetically alters gene expression. There is considerable evidence linking abnormal regulation of GJIC with the non-genotoxic steps of tumor promotion. We have worked with the Upham laboratory to devise a proteomics approach to detect early changes in protein abundance and post-translational modification due to PAHs.