吸烟是致肺癌的主要诱因。烟草致肺癌过程中，从损伤早期支气管-肺泡上皮细胞凋亡到细胞出现恶性转化的癌变过程的各个阶段，都会出现DNA甲基化和组蛋白修饰等特征性变化。我们前期研究发现长期染毒可以导致人永生化支气管上皮细胞(BEAS-2B)凋亡逃逸和一些表观遗传学改变。本研究在此基础上，拟对BEAS-2B细胞进行多剂量长期染毒，观察早期损伤和恶性转化后与凋亡相关的表观遗传学变化，同时对细胞表达的差异蛋白进行筛选和分析，观察组蛋白改变及DNA和蛋白交互作用，从中筛选出吸烟致癌在早期及各形成阶段的生物标志物。为阐明烟草致肺癌的健康危害提供科学依据, 并为肺癌的病因诊断和早期治疗提供新的生物指标和研究途径。

Cigarette smoking serves as the leading cause of lung cancer. More and more evidences showed that there are many characteristic changes in the carcinogenic process from initial injury to all stages of malignant transformation such as DNA methylation and histone modification. Our previous studies found that long term exposure to cigarette smoke can lead to cells apoptosis escape and relative epigenetic changes of human immortalized bronchial epithelial cells (BEAS-2B).Based on this study we will establish a cell model of multi-dose levels and long term exposure, observe early lesions and apoptosis-related epigenetic changes in the process of neoplastic transformation, screen and analyze the expression difference of cell protein, observe histone protein modfications and interactions of DNA and protein, and get biomarkers in the early stages and all stages of initiation, promotion and progression of lung cancer. The objective of project maybe is to clarify a scientific mechanism of lung cancer caused by cigarette smoke, and provide a new biomarkers and research approach on the diagnosis and early intervention of lung cancer.