title: Oxidative stress is implicated in arsenic-induced neural tube defects in chick embryos.
abstract: The potential of arsenic to induce neural tube defects (NTDs) remains a topic of controversy. In our previous study, oxidative stress and altered DNA methylation were observed in arsenic-exposed animal models. However, the correlation between these conditions was not fully understood. Therefore, our present aim was to determine whether arsenic exposure results in altered reactive oxygen species levels that affect DNA methylation and may contribute to NTDs in chick embryos. We demonstrated that arsenic-induced NTDs were associated with oxidative stress. Increased intracellular oxidative species and DNA methylation changes were observed following arsenic exposure. These changes were accompanied by a decrease in manganese superoxide dismutase activity. Furthermore, a significant decrease in DNA methyltransferase (DNMT) 1 and 3a expression was observed following arsenic exposure. The known antioxidant N-acetyl-l-cysteine, a known antioxidant, ameliorated global DNA hypomethylation and the decreased DNMT 1 and 3a expression observed during arsenic exposure. In addition, arsenic caused a significant decrease in S-adenosylmethionine (SAM) and significant increase in S-adenosylhomocysteine (SAH). This effect resulted in a significant reduction of the SAM/SAH ratio, which may also contribute to DNA hypomethylation. In conclusion, oxidative stress and reduction in SAM/SAH ratio during arsenic exposure in chick embryos seem to modulate DNA methylation and contribute to arsenic-induced NTDs via epigenetic mechanisms.
authors: Graduate School of Peking Union Medical College, Beijing, China.
authors: Zhong-Ji
authors: ZJ
authors: Han
authors: Ge
authors: G
authors: Song
authors: Yi
authors: Y
authors: Cui
authors: Hong-Fei
authors: HF
authors: Xia
authors: Xu
authors: X
authors: Ma
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D001151:Arsenic / Q000494:pharmacology*; D002642:Chick Embryo / Q000002:abnormalities* / Q000187:drug effects*; D044127:Epigenesis, Genetic; D005260:Female; D005979:Glutathione Peroxidase / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D009436:Neural Tube Defects / Q000139:chemically induced*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012435:S-Adenosylhomocysteine / Q000378:metabolism; D012436:S-Adenosylmethionine / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D012436:S-Adenosylmethionine; D012435:S-Adenosylhomocysteine; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D001151:Arsenic; D000111:Acetylcysteine