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使用體內(nèi)Pig-a基因突變?cè)囼?yàn)組合體系評(píng)估丙烯酸-2-乙基己酯的遺傳毒性

發(fā)布時(shí)間:2018-07-29 10:49
【摘要】:目的使用體內(nèi)Pig-a基因突變?cè)囼?yàn)組合體系進(jìn)一步評(píng)估丙烯酸-2-乙基己酯(2-ethylhexyl acrylate,2-EHA)在體內(nèi)的遺傳毒性。方法使用28日重復(fù)劑量染毒,聯(lián)合Pig-a基因突變?cè)囼?yàn)、彗星試驗(yàn)和微核試驗(yàn)檢測(cè)2-EHA的遺傳毒性。30只SPF級(jí)雄性SD大鼠隨機(jī)分為6組,即溶劑對(duì)照組(植物油),陽性對(duì)照組(N-乙基-N-亞硝基脲10 mg/kg)和2-EHA 100、200、400、800 mg/kg劑量組。連續(xù)灌胃28 d,于實(shí)驗(yàn)第0、15和29 d取尾靜脈血,使用流式細(xì)胞術(shù)測(cè)定突變成熟紅細(xì)胞和網(wǎng)織紅細(xì)胞數(shù)。末次灌胃6 h后取尾靜脈血進(jìn)行外周血彗星試驗(yàn),隨后處死動(dòng)物進(jìn)行骨髓紅細(xì)胞微核試驗(yàn)。結(jié)果實(shí)驗(yàn)后期,400 mg/kg和800 mg/kg 2-EHA組大鼠出現(xiàn)輕微中毒體征(束毛,精神萎靡)。Pig-a基因突變?cè)囼?yàn)結(jié)果顯示,各時(shí)間點(diǎn)4個(gè)劑量組成熟紅細(xì)胞和網(wǎng)織紅細(xì)胞突變細(xì)胞數(shù)均未見顯著增加。彗星試驗(yàn)結(jié)果顯示,各組間彗星尾長(zhǎng)和Olive尾矩差異無統(tǒng)計(jì)學(xué)意義。微核試驗(yàn)結(jié)果顯示,各組微核率差異無統(tǒng)計(jì)學(xué)意義。結(jié)論在該研究條件下,2-EHA在體內(nèi)Pig-a基因突變?cè)囼?yàn)、彗星試驗(yàn)和微核試驗(yàn)結(jié)果均為陰性,2-EHA可能不具有致突變性。
[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.
【作者單位】: 四川大學(xué)華西公共衛(wèi)生學(xué)院四川省食品安全監(jiān)測(cè)與風(fēng)險(xiǎn)評(píng)估重點(diǎn)實(shí)驗(yàn)室;
【基金】:國(guó)家自然科學(xué)基金面上項(xiàng)目(No.8157120809)
【分類號(hào)】:R114

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