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The selected epigenetic effects of aminomethylphosphonic acid, a primary metabolite of glyphosate on human peripheral blood mononuclear cells (in vitro).
Toxicology in Vitro ( IF 2.6 ) Pub Date : 2020-05-01 , DOI: 10.1016/j.tiv.2020.104878
Ewelina Woźniak 1 , Edyta Reszka 2 , Ewa Jabłońska 2 , Katarzyna Mokra 3 , Aneta Balcerczyk 4 , Bogumiła Huras 5 , Jerzy Zakrzewski 5 , Bożena Bukowska 3
Affiliation  

Aminomethylphosphonic acid (AMPA) is a primary metabolite of glyphosate and amino-polyphosphonate. We have determined the effect of AMPA on selected epigenetic parameters and major cell cycle drivers in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with AMPA at 0.5, 10 and 250 μM for 24 h. The performed analysis included: global DNA methylation by colorimetric measurement of 5-methylcytosine in DNA, methylation in the promoter regions of selected tumor suppressor genes (P16, P21, TP53) and proto-oncogenes (BCL2, CCND1) as well as the expression profile of the indicated genes by Real-Time PCR assays. The obtained results have revealed significant reduction of global DNA methylation level in PBMCs exposed to AMPA. Investigated xenobiotic changed methylation pattern of the P21 and TP53 suppressor gene promoters, but in case of other analyzed genes: P16, BCL2 and CCND1 no statistically significant changes have been noted. Gene profiling have shown that AMPA only changed the expression of CCND1. Summing up, our results have revealed a small potential disturbance in methylation processes and the absence of changes in expression of tested tumor suppressor genes (P16, P21, TP53) and protooncogenes (BCL2) in human PBMCs exposed to AMPA.

中文翻译:


氨甲基膦酸(草甘膦的主要代谢物)对人外周血单核细胞的选定表观遗传效应(体外)。



氨基甲基膦酸 (AMPA) 是草甘膦和氨基聚膦酸酯的主要代谢产物。我们已经确定了 AMPA 对人外周血单核细胞 (PBMC) 中选定的表观遗传参数和主要细胞周期驱动因素的影响。将细胞与 0.5、10 和 250 μM 的 AMPA 一起孵育 24 小时。进行的分析包括:通过比色测量 DNA 中 5-甲基胞嘧啶的整体 DNA 甲基化、选定肿瘤抑制基因(P16、P21、TP53)和原癌基因(BCL2、CCND1)启动子区域的甲基化以及表达谱通过实时 PCR 检测指定基因。获得的结果表明,暴露于 AMPA 的 PBMC 中整体 DNA 甲基化水平显着降低。研究发现外源物质改变了 P21 和 TP53 抑制基因启动子的甲基化模式,但对于其他分析基因:P16、BCL2 和 CCND1,没有发现统计学上显着的变化。基因分析表明 AMPA 仅改变 CCND1 的表达。总而言之,我们的结果揭示了暴露于 AMPA 的人 PBMC 中甲基化过程存在微小的潜在干扰,并且测试的肿瘤抑制基因(P16、P21、TP53)和原癌基因(BCL2)的表达没有变化。
更新日期:2020-05-01
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