Bukowska Bożena, Woźniak Ewelina, Sicińska Paulina, Mokra Katarzyna, Michałowicz Jaromir
Department of Biophysics of Environmental Pollution, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska Str. 141/143, 90-236 Lodz, Poland.
Laboratory of Tissue Immunopharmacology, Department of Internal Diseases and Clinical Pharmacology, Medical University of Lodz, Kniaziewicza 1/5, 91-347 Lodz, Poland.
Sci Total Environ. 2022 Dec 10;851(Pt 2):158259. doi: 10.1016/j.scitotenv.2022.158259. Epub 2022 Aug 27.
Glyphosate in the concentrations corresponding to environmental or occupational exposure has been shown to induce epigenetic changes potentially involved in carcinogenesis. This substance (1) changes the global methylation in various cell types and organisms and is responsible for the methylation of different promoters of individual genes, such as TP53 and P21 in human PBMCs, (2) decreases H3K27me3 methylation and H3 acetylation and increases H3K9 methylation and H4 acetylation in rats, (3) increases the expression of P16, P21, CCND1 in human PBMCs, and the expression of EGR1, JUN, FOS, and MYC in HEK293 cells, but decreases TP53 expression in human PBMCs, (4) changes the expression of genes DNMT1, HDAC3, TET1, TET2, TET3 involved in chromatin architecture, e.g. in fish Japanese medaka, (5) alters the expression of various small, single-stranded, non-coding RNA molecules engaged in post-transcriptional regulation of gene expression, such as miRNA 182-5p in MCF10A cells, miR-30 and miR-10 in mammalian stem cells, as well as several dozen of murine miRNAs. Epigenetic changes caused by glyphosate can persist over time and can be passed on to the offsprings in the next generation; in the third generation they can result in some disorders development, such as prostate disease or obesity. Some epigenetic mechanisms have indicated a potential risk of breast cancer development in human as a result of the exposure to glyphosate. It should be emphasized that the majority of reported epigenetic changes have not yet been associated with the final metabolic effects, which may depend on many other factors.
已表明，与环境或职业暴露相应浓度的草甘膦会诱导可能参与致癌作用的表观遗传变化。该物质（1）会改变多种细胞类型和生物体中的整体甲基化，并导致个别基因的不同启动子发生甲基化，如人外周血单核细胞中的TP53和P21；（2）会降低大鼠体内H3K27me3甲基化和H3乙酰化水平，并增加H3K9甲基化和H4乙酰化水平；（3）会增加人外周血单核细胞中P16、P21、CCND1的表达，以及HEK293细胞中EGR1、JUN、FOS和MYC的表达，但会降低人外周血单核细胞中TP53的表达；（4）会改变参与染色质结构的基因DNMT1、HDAC3、TET1、TET2、TET3的表达，如在日本青鳉鱼中；（5）会改变参与基因表达转录后调控的各种小的单链非编码RNA分子的表达，如MCF10A细胞中的miRNA 182 - 5p、哺乳动物干细胞中的miR - 30和miR - 10，以及几十种小鼠miRNA。草甘膦引起的表观遗传变化会随时间持续存在，并可传递给下一代的后代；在第三代中，它们可能导致某些疾病的发展，如前列腺疾病或肥胖症。一些表观遗传机制表明，接触草甘膦可能会使人患乳腺癌的风险增加。应当强调的是，大多数已报道的表观遗传变化尚未与最终的代谢效应相关联，而最终代谢效应可能取决于许多其他因素。
