EPIGENIC TOXICITY OF POLYCYCLIC AROMATIC HYDROCARBONS

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 多环芳烃（PAHs）是烟草烟雾中丰富的成分，与癌症形成有关。大量的研究表明，这些化合物会引起遗传损伤，从而导致癌症。然而，癌症不仅仅是不可逆的诱变事件的结果，而且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。间隙连接细胞间通讯（GJIC）集中调节信号转导途径，表观遗传学改变基因表达。有相当多的证据将GJIC的异常调节与肿瘤促进的非遗传毒性步骤联系起来。我们与厄本实验室合作，设计了一种蛋白质组学方法来检测由于多环芳烃引起的蛋白质丰度和翻译后修饰的早期变化。

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.