ORIGINAL ABSTRACT

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.