Figure 3.

Effects of xenobiotic-induced redox alterations on epigenetics. (A) During embryonic development, xenobiotics may increase the production of ROS in the embryo, exposing proliferating cells to increased oxidative stress. Under oxidizing conditions, the shunting of sulfur from the methionine cycle to the production of GSH is observed. Additionally, oxidative stress also inhibits SAM synthetase. Thus, xenobiotics that interfere with cellular redox balance may change SAM availability when a delicate balance is needed to regulate the epigenotype of differentiating cells. (B) Cellular redox balance also interferes with demethylation enzymes, such as the JmjC superfamily and TET1, as well as with prolyl hydroxylases/hypoxia-inducible factors (HIF) systems, altering epigenetic settings during development and consequently altering gene expression. (C) Oxidation of methylated CpG sites due to the effect of xenobiotics can create either 5hmC or 8-OG and alters MBP binding kinetics, interfering with gene expression and re-methylation of the daughter DNA strands after cellular division.