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Evaluation of Potential DNA-Damaging Effects of Nitenpyram and Imidacloprid in Human U937-Cells Using a New Statistical Approach to Analyse Comet Data
Exposure and Health ( IF 4.5 ) Pub Date : 2019-10-31 , DOI: 10.1007/s12403-019-00328-6
Erik Bivehed , Anton Gustafsson , Anders Berglund , Björn Hellman

Even if the two neonicotinoids nitenpyram and imidacloprid have been considered safe for humans, their potential genotoxicity still remains a matter of discussion. The DNA-damaging effects of these two compounds were therefore evaluated in a lymphoma cell line of human origin (U-937) using the comet assay after 3-h exposure to up to 50 μM, with or without metabolic activation using S9 from human liver. The comet data were analysed using a traditional one-way ANOVA after pooling the data on cellular level, and a new alternative approach we have called Uppsala Comet Data Analysis Strategy (UCDAS). UCDAS is a proportional odds model tailored to continuous outcomes, taking the number of pooled cultures, slides and cells into consideration in the same analysis. To the best of our knowledge, the UCDAS approach when analysing comet data has never been presented before. Without metabolic activation, no increase in DNA damage was observed in the neonicotinoide-exposed cells. Nitenpyram was also without DNA-damaging effects when S9 was added. However, in the presence of S9, imidacloprid was found to increase the level of DNA damage. Whereas the ANOVA showed an increase (P < 0.001) both at 5 and 50 μM, UCDAS showed an increase only at the lowest concentration (P < 0.001). Based on these findings, the two neonicotinoids seem to be of little concern when it comes to their potential genotoxicity. However, since the U-937 cells were rather resistant to our positive controls, they may not be the best cells to use when evaluating potential genotoxicity of chemicals.

中文翻译:

使用新的统计方法分析彗星数据,评估烯啶虫胺和吡虫啉对人类U937细胞的潜在DNA损伤作用

即使两个新烟碱类药物硝苯并吡虫啉和吡虫啉对人类都是安全的,但它们潜在的遗传毒性仍然是讨论的问题。因此,在暴露至高达50μM的条件下3小时后,使用彗星测定法在人类起源的淋巴瘤细胞系(U-937)中使用彗星测定法评估了这两种化合物的DNA损伤作用,无论是否使用人肝中的S9进行代谢激活。在细胞水平上汇总数据后,使用传统的单向方差分析对彗星数据进行了分析,而一种新的替代方法我们称为Uppsala彗星数据分析策略(UCDAS)。UCDAS是为连续结果量身定制的比例赔率模型,在同一分析中考虑了合并培养物,载玻片和细胞的数量。据我们所知,分析彗星数据时使用的UCDAS方法从未出现过。没有代谢活化,在暴露于新烟碱的细胞中未观察到DNA损伤的增加。添加S9时,乙炔吡喃也没有DNA破坏作用。然而,在存在S9的情况下,发现吡虫啉增加了DNA损伤的水平。而方差分析显示P  <0.001)在5和50μM时,UCDAS仅在最低浓度下显示增加(P  <0.001)。基于这些发现,当涉及到其潜在的基因毒性时,这两种新烟碱类化合物似乎很少引起关注。但是,由于U-937细胞对我们的阳性对照具有相当的抵抗力,因此当评估化学物质的潜在遗传毒性时,它们可能不是最好的细胞。
更新日期:2019-10-31
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