维生素C对有机磷类和拟除虫菊酯类农药联合染毒致小鼠遗传毒性的拮抗作用

Antagonistic effect of vitamin C on genotoxicity induced by joint exposure to organophosphorus and pyrethroid pesticides in mice

目的探讨维生素C(Vit C)对有机磷类和拟除虫菊酯类农药联合致小鼠体细胞和生殖细胞突变的拮抗作用。方法将60只健康SPF级昆明小鼠随机分为6组,每组10只,雌雄各半,分别为农药联合(0.3 mg/kg马拉硫磷+0.01 mg/kg毒死蜱+0.02 mg/kg氯氰菊酯+0.02 mg/kg高效氯氟氰菊酯)组和低(100 mg/kg)、中(200 mg/kg)、高剂量(400 mg/kg)Vit C+农药联合组及溶剂对照(玉米油)组、阳性对照(第1、2天不做任何处理,第3、4天腹腔注射40 mg/kg环磷酰胺)组;采用灌胃方式进行染毒农药,连续染毒4 d;各剂量Vit C+农药联合组先单独灌胃染毒Vit C溶液,间隔1 h后,再给予农药。于染毒结束次日,进行小鼠骨髓嗜多染红细胞微核试验。另将30只雄性小鼠随机分为6组,每组5只,分别为农药联合组和低、中、高剂量Vit C+农药联合组及溶剂对照(玉米油)组、阳性对照(腹腔注射40 mg/kg环磷酰胺)组。采用灌胃方式进行染毒农药,连续染毒5 d;各剂量Vit C+农药联合组先单独灌胃染毒Vit C溶液,间隔1 h后,再给予农药。于首次染毒后第35天,进行小鼠精子畸形试验。结果与溶剂对照组比较,农药联合组和各剂量Vit C+农药联合组小鼠的骨髓细胞微核率升高,差异均有统计学意义(P<0.05)。经各剂量Vit C+农药联合作用后,小鼠骨髓细胞微核率下降,均低于农药联合组,差异有统计学意义(P<0.05)。各组小鼠的PCE/NCE值间比较,差异无统计学意义(P>0.05)。与溶剂对照组比较,农药联合组和低、中剂量Vit C+农药联合组小鼠的精子畸形率升高,差异均有统计学意义(P<0.05)。中、高剂量Vit C+农药联合组小鼠的精子畸形率均低于农药联合组,差异有统计学意义(P<0.05);且随着Vit C染毒剂量的升高,农药联合暴露小鼠的骨髓细胞微核率和精子畸形率均呈下降趋势。结论马拉硫磷、毒死蜱、氯氰菊酯和高效氯氟氰菊酯联合经口染毒对小鼠具有遗传毒性效应,适量Vit C对4种农药联合致体细胞和生殖细胞突变具有一定的拮抗作用。

Objective To investigate the antagonism of vitamin C on mutation of somatic and germ cells in mice induced by joint exposure to organophosphorus and pyrethroid pesticides. Methods A total of 60 healthy SPF grade Kunming mice were randomly divided in six groups, 10 in each group, half male and half female, pesticide combination group（0.3 mg/kg body weight malathion＋0.01 mg/kg body weight chlorpyrifos＋0.02 mg/kg body weight cypermethrin＋0.02 mg/kg body weight lambdacyhalothrin）, low（100 mg/kg body weight）, moderate（200 mg/kg body weight）, high dose（400 mg/kg body weight） Vit C ＋pesticide combination group and solvent control（corn oil） group, positive control group.The positive control group received no treatment at the 1 st and 2 nd day during the experiment,and was given intraperitoneal injection of 40 mg/kg body weight cyclophosphamide at the 3 rd and 4 th day during the experiment. The pesticides exposure was conducted through gavage, for five consecutive days.The mice in Vit C＋pesticide combination group were administered with Vit C alone by gavage, followed by an interval of 1 h before pesticides were given.After exposure, micronucleus test was performed on bone marrow polychromatic erythrocytes in mice. Another 30 male mice were randomly divided in six groups, five in each, pesticide combination group and the low, moderate and high doses of Vit C ＋pesticide combination group and solvent control（corn oil） group and the positive control（i.p. 40 mg/kg body weight cyclophosphamide, i.p.） group. The pesticides exposure were administered by gavage for five days.The mice in Vit C＋pesticide combination groups were administered with Vit C alone by gavage, followed by an interval of 1 h before pesticides were given. At the 35 th day after the first exposure, a mouse sperm abnormality test was performed. Results Compared with the solvent control group, the micronucleus rates of bone marrow cells in the pesticide combination group and each Vit C＋pesticide combination group increased significantly（P〈0.05）. As for the combined effects of various doses of Vit C＋pesticides, the micronucleus rate of bone marrow cells in mice decreased, which were significantly lower than that of combined group of pesticides（P〈0.05）. There was no significant difference in PCE/NCE between groups（P〉0.05）. Compared with the solvent control group, the sperm abnormality rates in the pesticide combination group and the low and moderate doses of Vit C＋pesticide combination group increased significantly（P〈0.05）. The rates of sperm abnormality in the moderate and high doses of Vit C ＋pesticide combination group were significantly lower than that of the pesticide combination group（P〈0.05）. With the increase of Vit C exposure dose, the micronucleus rate of bone marrow cells and the sperm abnormality rate in the pesticides combined exposure of mice showed a downward trend. Conclusion Malathion,chlorpyrifos,cypermethrin and lambda-cyhalothrin in combination has oral genotoxic effect in mice and appropriate Vit C may present certain antagonistic effect.