3-氯-4-二氯甲基-5-羟基-2(5氢)-呋喃酮对小鼠的遗传毒性与氧化损伤的关系

Study on Oxidative Damage and Genotoxicity Induced by MX in Mice

背景与目的 :研究饮水氯化消毒副产物3_氯_4_二氯甲基_5_羟基_2(5氢)_呋喃酮(3_chloro_4_(dichloromethyl)_5_hydroxy_2[5H]_furanone,MX)对小鼠的遗传毒性与氧化损伤的诱导。 材料与方法 :昆明种小鼠随机分为4组 ,即溶剂对照组与低、中、高3个MX剂量组(11、33、100mg/kg) ,受试小鼠经腹腔注射染毒3h后处死。应用单细胞凝胶电泳技术(SCGE ,彗星分析)检测小鼠肝、肾、小肠的DNA损伤 ,并测定小鼠肝、肾和小肠中脂质过氧化主要终产物丙二醛(Malondialdehyde,MDA)的含量。结果 :随着MX浓度的增加 ,小鼠肝、肾、小肠中MDA含量与其细胞的Olive尾矩明显升高 ,且呈现较好的剂量依赖性。与溶剂对照组比较 :①MX各剂量组小肠细胞Olive尾距均显著性增加 ,肝、肾细胞的Olive尾距在MX较高剂量时有显著性增加 ;②中、高剂量组小鼠肝组织中MDA含量显著性升高 ,高剂量组小鼠肾和小肠组织中MDA含量明显升高 ,差异有显著性意义。肝、肾、小肠MDA含量与Olive尾矩均呈明显正相关。结论 :MX可引发哺乳动物多种脏器的脂质过氧化反应增强 ;并能引起细胞DNA损伤。MX导致机体组织的氧化损伤可能在细胞遗传毒性作用中起重要作用。

BACKGROUND&AIM: To study the oxidative damage and genotoxicity induced by3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone(MX)in mice,and to explore the possible mechanism of genotoxicity caused by MX. MATERIAL AND METHODS: Mice were divided into four groups including solvent control group and three MX-treated groups(11,33,100mg/kg).Test substances were administered intraperitoneal(i.p.)and mice were sacrificed3hours after the treatment.DNA damage and malondialdehyde(MDA)in livers,kidneys and small intestines were examined using the alkaline single-cell gel electrophoresis(SCGE,comet assay)and test kit. RESULTS: It was observed that MX yielded significant increase in the DNA damage in small intestines of mice at all dosage and in liver and kidney of mice at higher dosage compared with the solvent control(P<0.01).The concentration of MDA in livers,kidneys and small intestines of mice in the highest MX-exposed groups were significantly higher than that in solvent control group(P<0.05).There was a significant correlation between MDA and Olive tail moment in liver,kidney and small intestines. CONCLUSION: MX could induce obvious DNA damage and oxidative stress in multiple organs of mice.The cell oxidative damage might be one of the primary mechanisms of genotoxicity of MX.