敌敌畏、乐果和马拉硫磷诱导HepG2细胞DNA损伤的实验研究

目的：评价敌敌畏（dichlorvos,DDVP）、乐果（dimethoate,DM）和马拉硫磷（malathion,Mal）3种常用有机磷农药单独及两两组合下诱导HepG2细胞DNA损伤效应,并阐明联合作用模式。方法：3种有机磷农药分别单独染毒HepG2细胞4h,联合效应研究采用析因设计分别在高剂量水平和低剂量水平下将3种农药两两混合染毒,同时设溶剂对照（DMSO作用4h）和阳性对照（0.5μmol/ml重铬酸钾染毒2h）,染毒结束后进行彗星试验,采集图像并用CASP软件分析,选择尾部DNA百分比、彗星尾长（tail length,TL）和Olive尾矩（Olive tail moment,OTM）表示DNA损伤强度。结果：3种有机磷农药单独作用时,较高剂量组的尾部DNA百分比、TL和OTM均显著高于对照组（P〈0.01）;析因分析联合效应结果表明,较低剂量水平下,DDVP与DM之间无交互作用（P〉0.05）,DDVP与Mal之间以及DM与Mal之间存在交互作用（P〈0.01）,交互方式均为协同;在较高剂量水平,3种农药两两间均存在交互作用（P〈0.05）,交互方式均为拮抗。结论：敌敌畏、乐果和马拉硫磷单独及两两联合作用均可致DNA损伤,在低剂量和高剂量水平下,存在不同的联合作用模式。

DNA damage induced by three organophosphate pesticides

OBJECTIVE: To invesgate the genotoxicity of dichlorvos(DDVP), dimethoate(DM) and malathion(Mal) in HepC2 cells alone and in combination, and to elucidate the combined genotoxic effects. METHODS: Comet assay (single cell gel electrophoresis assay) was adopted to evaluate the genotoxicity of dichlorvos(DDVP), dimethoate(DM) and malathion(Mal), the images were collected and then analyzed by CASP software. The 2× 2factorial analysis experiment was used to investigate their combined genotoxic effects. RESULTS: DDVP, DM and Mai all induced obvious DNA damage in HepG2 cells after treatmemt for 4 h. At the two higher concentrations of each pesticide, these parameters (percent of Tail DNA, Tail Length and Olive Tail Moment) measuring DNA damage were significantly more serious compared with solvent control. Factorial ANOVA revealed that at lower mixed dose, no interaction was noted between DDVP and DM. But DDVP and Mal, also DM and Mal both exerted synergistic effect; while at higher mixed dose, antagonistic effect were found between DDVP and DM, DDVP and Mal, as well as DM and Mal. CONCLUSION: DDVP,DM and Mal could induce DNA damage both alone and in combination, but the combined effects varied with the mixture concentration.