University of Lodz, Faculty of Biology and Environmental Protection, Department of Biophysics of Environmental Pollution, Pomorska Str. 141/143, 90-236 Lodz, Poland; Medical University of Lodz, Department of Internal Diseases and Clinical Pharmacology, Laboratory of Tissue Immunopharmacology, Kniaziewicza Str. 1/5, 91-347 Lodz, Poland.
Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Teresy Str. 8, 91-348 Lodz, Poland.
Toxicol In Vitro. 2020 Mar;63:104736. doi: 10.1016/j.tiv.2019.104736. Epub 2019 Nov 18.
We have determined the effect of glyphosate on selected epigenetic parameters and major cell cycle drivers in human peripheral blood mononuclear cells (PBMCs). The cells were incubated with glyphosate at 0.5, 10 and 100 μM. The analysis included: global DNA methylation, methylation in the promoter regions of tumor suppressor genes (P16, P21, TP53) and proto-oncogenes (BCL2, CCND1) by the Real-Time PCR and the expression profile of the indicated genes by Real-Time PCR. The obtained results have revealed significant reduction of global DNA methylation level in PBMCs exposed to glyphosate. Tested compound changed methylation pattern of the P21 and TP53 suppressor gene promoters, but in case of other analyzed genes: P16, BCL2 and CCND1 we did not identify any statistically significant changes. Gene profiling showed that glyphosate changed the expression of genes involved in the regulation of cell cycle and apoptosis. Glyphosate decreased expression of P16 and TP53 as well as an increase in the expression of BCl2, CCND1 and P21. Summing up, our results have shown a potential disturbance in methylation processes and gene expression in human PBMCs exposed to glyphosate, but the observed changes do not prejudge about the final metabolic effects, which are depended on many other factors.
我们已经确定了草甘膦对人外周血单个核细胞（PBMCs）中选定的表观遗传参数和主要细胞周期驱动因子的影响。将细胞用草甘膦在 0.5、10 和 100µM 下孵育。分析包括：通过实时 PCR 分析全基因组 DNA 甲基化、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，以及通过实时 PCR 分析所述基因的表达谱。获得的结果表明，暴露于草甘膦的 PBMCs 中全基因组 DNA 甲基化水平显著降低。测试化合物改变了 P21 和 TP53 抑制基因启动子的甲基化模式，但在其他分析的基因：P16、BCL2 和 CCND1 中，我们没有发现任何具有统计学意义的变化。基因谱分析表明，草甘膦改变了参与细胞周期和细胞凋亡调节的基因的表达。草甘膦降低了 P16 和 TP53 的表达，同时增加了 BCl2、CCND1 和 P21 的表达。总之，我们的结果表明，暴露于草甘膦的人 PBMCs 中甲基化过程和基因表达可能受到干扰，但观察到的变化并不能预先判断最终的代谢效应，这取决于许多其他因素。
