关键词: 有机污染物, 细胞恶性转化, MGMT, 高甲基化

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.

Key words: organic contaminant, malignant transformation, MGMT gene, hypermethylation