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使用体内Pig-a基因突变试验组合体系评估丙烯酸-2-乙基己酯的遗传毒性

发布时间:2018-07-29 10:49
【摘要】:目的使用体内Pig-a基因突变试验组合体系进一步评估丙烯酸-2-乙基己酯(2-ethylhexyl acrylate,2-EHA)在体内的遗传毒性。方法使用28日重复剂量染毒,联合Pig-a基因突变试验、彗星试验和微核试验检测2-EHA的遗传毒性。30只SPF级雄性SD大鼠随机分为6组,即溶剂对照组(植物油),阳性对照组(N-乙基-N-亚硝基脲10 mg/kg)和2-EHA 100、200、400、800 mg/kg剂量组。连续灌胃28 d,于实验第0、15和29 d取尾静脉血,使用流式细胞术测定突变成熟红细胞和网织红细胞数。末次灌胃6 h后取尾静脉血进行外周血彗星试验,随后处死动物进行骨髓红细胞微核试验。结果实验后期,400 mg/kg和800 mg/kg 2-EHA组大鼠出现轻微中毒体征(束毛,精神萎靡)。Pig-a基因突变试验结果显示,各时间点4个剂量组成熟红细胞和网织红细胞突变细胞数均未见显著增加。彗星试验结果显示,各组间彗星尾长和Olive尾矩差异无统计学意义。微核试验结果显示,各组微核率差异无统计学意义。结论在该研究条件下,2-EHA在体内Pig-a基因突变试验、彗星试验和微核试验结果均为阴性,2-EHA可能不具有致突变性。
[Abstract]:Objective to further evaluate the genotoxicity of 2-ethylhexyl acrylic acid (2-ethylhexyl) in vivo using Pig-a gene mutation assay. Methods 30 male SD rats of SPF grade were randomly divided into 6 groups by 28 days repeated dose exposure, combined with Pig-a gene mutation test, comet assay and micronucleus test to detect the genotoxicity of 2-EHA. They were solvent control group (vegetable oil), positive control group (N- ethyl-N-nitroso 10 mg/kg) and 2-EHA 100200400800 mg/kg group. At the 15th and 29th days of the experiment, the blood of caudal vein was collected and the number of mutant mature erythrocytes and reticulocytes were measured by flow cytometry. The tail vein blood was taken for comet assay in peripheral blood after the last gastric perfusion for 6 hours, and then the bone marrow erythrocyte micronucleus test was performed on the animals. Results in the later stage of the experiment, the rats in the 400 mg/kg and 800 mg/kg 2-EHA groups showed slight toxic signs (bundle hair, mental retardation) .Pig-a gene mutation test showed that the number of mature erythrocytes and reticulocyte mutant cells did not increase significantly in the four dose groups at each time point. Comet assay showed that there was no significant difference in comet tail length and Olive tail moment among the groups. The results of micronucleus test showed that there was no significant difference in micronucleus rate among groups. Conclusion under this condition, the results of Pig-a gene mutation test, comet assay and micronucleus test in vivo may not be mutagenic.
【作者单位】: 四川大学华西公共卫生学院四川省食品安全监测与风险评估重点实验室;
【基金】:国家自然科学基金面上项目(No.8157120809)
【分类号】:R114

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