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
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摘要
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.
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.
引文
[1]邹继红,季光辉,宋欣鑫,等.蔬菜中有机氯和拟除虫菊酯农药残留量的测定[J].沈阳药科大学学报,2007,24(3):156-159.
[2]马爱国,刘四朝.不同剂量维生素C对DNA氧化损伤影响的研究[J].营养学报,2001,23(1):12-14.
[3]黄幸纾,陈星若.环境化学物致突变、致畸、致癌试验方法[M].杭州:浙江科学技术出版社,1985:266.
[4]张彩虹,陈剑刚,白艳玲.珠海市农贸市场蔬果茶叶中农药残留现状及其防治建议[J].中国热带医学,2008,8(5):863-864.
[5]李树飞,刘英华,张大龙,等.有机磷与拟除虫菊酯类混配农药对小鼠自然杀伤细胞的免疫毒性[J].环境与健康杂志,2015,32(10):877-880.
[6]周殿明,张大龙,张静,等.有机磷与拟除虫菊酯类混配农药对小鼠细胞免疫毒性作用及机制[J].环境与健康杂志,2015,32(9):787-790.
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[8]何智敏,许滋宁.2009-2010年南通市售蔬菜、水果中农药残留状况调查分析[J].江苏预防医学,2012,23(2):63-64.
[9]付宇,陈彦凤,刘长福,等.2010年黑龙江省市售蔬菜中有机磷农药的监测结果[J].职业与健康,2012,28(19):2372-2373.
[10]李倩,房宁,赵劲松.2011年北京市大兴区市售蔬菜农药污染状况分析[J].中国卫生检验杂志,2012,22(11):2753-2754.
[11]郑建峰.德州市部分蔬菜中有机磷农药残留调查[J].环境与健康杂志,2012,29(7):626.
[12]罗赟,向仲朝,岳蕴瑶.绵阳市蔬菜、水果和粮食中四种有机氯农药残留量调查[J].中国卫生检验杂志,2012,22(8):1950-1952.
[13]田礼钦,周雅,张宁.苏州市蔬菜中有机磷农药残留情况分析[J].江苏预防医学,2012,23(3):62-63.
[14]胡黎黎,邱宏,顾万江,等.重庆市2009年蔬菜、水果、新鲜食用菌、茶叶农药残留监测结果分析[J].现代预防医学,2012,39(3):3213-3215.
[15]张桥.卫生毒理学基础[M].3版.北京:人民卫生出版社,2003:254.
[16]文一,刘伟江,赵康平,等.氧化乐果和毒死蜱混剂对大鼠雄性生殖功能的联合毒性[J].生态毒理学报,2013,8(6):945-954.
[17]安连杰,冯小雨,巴婧,等.阿维菌素与毒死蜱联合作用对大鼠脂质过氧化的影响[J].工业卫生与职业病,2013,39(6):343-347.
[18]戈果,余资江,谢骐骥,等.维生素E和维生素C联合染毒对慢性镉中毒小鼠脑组织黑质神经元的保护作用[J].环境与健康杂志,2011,28(11):974-977.
[19]朱姝,吴雨龙,张边江.铅和维生素C染毒对果蝇寿命和生殖力以及抗氧化系统的影响[J].环境与健康杂志,2011,28(11):981-983.
[20]Das B,Maity PC,Sil AK.Vitamin C forestalls cigarette smoke induced NF-κB activation in alveolar epithelial cells[J].Toxicol Lett,2013,220:76-81.
[21]Das RL,Giri S,Singh S,et al.Effects of radiation and vitamin C treatment on metronidazole genotoxicity in mice[J].Mutat Res/Genetic Toxicol Environ Mutat,2013,753:65-71.
[22]王亚宁,关秋艳,谢吕,等.维生素C对纳米二氧化钛致突变的保护作用研究[J].工业卫生与职业病,2014,10(3):187-190.
[2]马爱国,刘四朝.不同剂量维生素C对DNA氧化损伤影响的研究[J].营养学报,2001,23(1):12-14.
[3]黄幸纾,陈星若.环境化学物致突变、致畸、致癌试验方法[M].杭州:浙江科学技术出版社,1985:266.
[4]张彩虹,陈剑刚,白艳玲.珠海市农贸市场蔬果茶叶中农药残留现状及其防治建议[J].中国热带医学,2008,8(5):863-864.
[5]李树飞,刘英华,张大龙,等.有机磷与拟除虫菊酯类混配农药对小鼠自然杀伤细胞的免疫毒性[J].环境与健康杂志,2015,32(10):877-880.
[6]周殿明,张大龙,张静,等.有机磷与拟除虫菊酯类混配农药对小鼠细胞免疫毒性作用及机制[J].环境与健康杂志,2015,32(9):787-790.
[7]Komuta N,Bagley E,Nedopitanskaya N.Genotoxic effects of pesticides[J].Environ Pathol Toxicol Oncol,1996,15:75-78.
[8]何智敏,许滋宁.2009-2010年南通市售蔬菜、水果中农药残留状况调查分析[J].江苏预防医学,2012,23(2):63-64.
[9]付宇,陈彦凤,刘长福,等.2010年黑龙江省市售蔬菜中有机磷农药的监测结果[J].职业与健康,2012,28(19):2372-2373.
[10]李倩,房宁,赵劲松.2011年北京市大兴区市售蔬菜农药污染状况分析[J].中国卫生检验杂志,2012,22(11):2753-2754.
[11]郑建峰.德州市部分蔬菜中有机磷农药残留调查[J].环境与健康杂志,2012,29(7):626.
[12]罗赟,向仲朝,岳蕴瑶.绵阳市蔬菜、水果和粮食中四种有机氯农药残留量调查[J].中国卫生检验杂志,2012,22(8):1950-1952.
[13]田礼钦,周雅,张宁.苏州市蔬菜中有机磷农药残留情况分析[J].江苏预防医学,2012,23(3):62-63.
[14]胡黎黎,邱宏,顾万江,等.重庆市2009年蔬菜、水果、新鲜食用菌、茶叶农药残留监测结果分析[J].现代预防医学,2012,39(3):3213-3215.
[15]张桥.卫生毒理学基础[M].3版.北京:人民卫生出版社,2003:254.
[16]文一,刘伟江,赵康平,等.氧化乐果和毒死蜱混剂对大鼠雄性生殖功能的联合毒性[J].生态毒理学报,2013,8(6):945-954.
[17]安连杰,冯小雨,巴婧,等.阿维菌素与毒死蜱联合作用对大鼠脂质过氧化的影响[J].工业卫生与职业病,2013,39(6):343-347.
[18]戈果,余资江,谢骐骥,等.维生素E和维生素C联合染毒对慢性镉中毒小鼠脑组织黑质神经元的保护作用[J].环境与健康杂志,2011,28(11):974-977.
[19]朱姝,吴雨龙,张边江.铅和维生素C染毒对果蝇寿命和生殖力以及抗氧化系统的影响[J].环境与健康杂志,2011,28(11):981-983.
[20]Das B,Maity PC,Sil AK.Vitamin C forestalls cigarette smoke induced NF-κB activation in alveolar epithelial cells[J].Toxicol Lett,2013,220:76-81.
[21]Das RL,Giri S,Singh S,et al.Effects of radiation and vitamin C treatment on metronidazole genotoxicity in mice[J].Mutat Res/Genetic Toxicol Environ Mutat,2013,753:65-71.
[22]王亚宁,关秋艳,谢吕,等.维生素C对纳米二氧化钛致突变的保护作用研究[J].工业卫生与职业病,2014,10(3):187-190.