分子伴侣热休克蛋白90（HSP90）是重要的信号转导因子，可介导细胞自噬。已有研究表明：苯并（a）芘（BaP）是重要的环境致癌物之一；肿瘤的发生发展与自噬密切相关。但BaP与自噬的关系及HSP90在BaP引起自噬之间的作用尚未见文献报道，本课题拟采用RT-PCR、Western blot、彗星实验、siRNA干扰、裸鼠皮下成瘤实验等技术探讨BaP是否通过以下三个途径影响自噬：1.BaP激活AhR信号通路，使HIF-1表达增加并通过HSP90调节自噬；2.BaP的代谢产物与DNA双链结合引起基因组的不稳定性，通过HSP90介导自噬；3.Bap与AhR结合时，HSP90与AhR分离释放到胞浆进一步影响自噬。通过以上研究明确HSP90在BaP诱导自噬中的分子机理，为BaP致癌机理的研究和HSP90作为抗癌药物的靶标研究奠定一定的基础。

As an important signal transducer, heat shock protein 90（HSP90）can mediate the process of autophagy. Existing researches have indicated that Benzo(a)pyrene (BaP) is one of the major environmental carcinogens. In addition, tumorigenesis relates closely with autophagy. However, the relationship between BaP and autophagy or the role of HSP90 in autophagy induced by BaP have not been reported yet. RT-PCR、Western blot, comet assay，siRNA interference，xenograft assay etc will be used in this project to study whether BaP influences autophagy through the following three approaches: 1. HSP90 mediates autophagy with up-regulated HIF-1 expression by AhR signaling pathway activation after BaP treatment. 2.The metabolites of BaP induce gene instability as it can bind with DNA double strand and then mediate autophagy via HSP90. 3. Once BaP combines with AhR，HSP90 will separate from AhR and be released to cytoplasm，which further influences autophagy. The molecular mechanism of BaP on HSP90 mediated autophagy will be clarified by the above experiments. This will lay a foundation for studies about carcinogenic mechanisms of BaP and prospect of HSP90 as a target for anti-cancer drugs.