title: Dichlorvos-induced cell cycle arrest and DNA damage repair activation in primary rat microglial cells.
abstract: Dichlorvos, an organophosphate (OP), is known to cause oxidative stress in the central nervous system (CNS). Previously we have shown that dichlorvos treatment promoted the levels of proinflammatory molecules and ultimately induced apoptotic cell death in primary microglial cells. Here we studied the effect of dichlorvos on crucial cell cycle regulatory proteins and the DNA damage sensor ataxia-telangiectasia mutated (ATM). We found a significant increase in p53 and its downstream target, p21, levels in dichlorvos-treated microglial cells compared with control cells. Moreover, dichlorvos exposure promoted the levels of different cell cycle regulatory proteins. These results along with flow cytometry results suggested that primary microglial cells were arrested at G1 and G2/M phase after dichlorvos exposure. We have shown in a previous study that dichlorvos can induce DNA damage in microglia; here we found that microglial cells also tried to repair this damage by inducing a DNA repair enzyme, i.e., ATM. We observed a significant increase in the levels of ATM after dichlorvos treatment compared with control.
authors.affiliation: Department of Biochemistry, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
authors.forename: Aditya
authors.initials: A
authors.lastname: Sunkaria
authors.forename: Willayat Yousuf
authors.initials: WY
authors.lastname: Wani
authors.forename: Deep Raj
authors.initials: DR
authors.lastname: Sharma
authors.forename: Kiran Dip
authors.initials: KD
authors.lastname: Gill
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059447:Cell Cycle Checkpoints / Q000187:drug effects* / Q000235:genetics; D002478:Cells, Cultured; D004249:DNA Damage / Q000187:drug effects* / Q000235:genetics; D004260:DNA Repair / Q000187:drug effects* / Q000235:genetics; D004006:Dichlorvos / Q000633:toxicity*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D010755:Organophosphates / Q000633:toxicity; D061251:Primary Cell Culture; D051381:Rats; D017208:Rats, Wistar
chemical_list: D010755:Organophosphates; D004006:Dichlorvos