癌变·畸变·突变2012，Vol.24Issue(3)：161-165,5.DOI:10.3969/j.issn.1004-616x.2012.03.001
癌症高发区环境水样有机提取物诱导L-02细胞转化及其表观遗传学机制
Transformation and epigenetic changes of L-02 cells by organic extracts of water environment
摘要
Abstract
OBJECTIVE: To assess the carcinogenicity of organic extracts of water environment and elucidate the possible epigenetic mechanism. METHODS: Surface water of X river and groundwater of Y and Z villages were collected, and solid phase extraction cartridges were usedto extract organic contaminants from the water samples. Trypan blue dye exclusion method was conducted to examine the cytotoxicity of the extracts, whilst the organic extracts-induced DNA breakage was measured using single cell gel electrophoresis assay. After long term treatment of the extracts, soft agar assay and tumor formation of immunodeficient mice were performed to test the carcinogenicity. Methylation-specific PCR (MSP) was employed to determine the methylation status of MGMT gene in both transformed cells and control L-02 cell line. Meanwhile, the Mrna and protein levels of MGMT were examined, using RT-q-PCR and Western blot assays. RESULTS: The organic extracts showed cytotoxicity against the L-02 cells and could induce DNA breakage. L-02 cells were malignantly transformed by the three organic extracts. Compared with the control cells, MGMT gene showed hypermethylation in promoter and it was down-regulated in transformed cells (P<0.05). CONCLUSION: The organic extracts of the water environment exhibited carcinogenicity and hypermethylation of MGMT promoter may be accountable.关键词
有机污染物/细胞恶性转化/MGMT/高甲基化Key words
organic contaminant/malignant transformation/MGMT gene/hypermethylation分类
医药卫生引用本文复制引用
张世鑫,张波,王庆,陈雯,邢秀梅,孙新,何民富,马璐,杨萍,肖勇梅,何志妮,李道传..癌症高发区环境水样有机提取物诱导L-02细胞转化及其表观遗传学机制[J].癌变·畸变·突变,2012,24(3):161-165,5.基金项目
国家杰出青年基金项目(30925029),国家自然科学基金项目(81072284),国家863计划项目(2008AA062504) （30925029）
