title: Endosulfan induces cell dysfunction through cycle arrest resulting from DNA damage and DNA damage response signaling pathways.
abstract: Our previous study showed that endosulfan increases the risk of cardiovascular disease. To identify toxic mechanism of endosulfan, we conducted an animal study for which 32 male Wistar rats were randomly and equally divided into four groups: Control group (corn oil only) and three treatment groups (1, 5 and 10mgkg-1·d-1). The results showed that exposure to endosulfan resulted in injury of cardiac tissue with impaired mitochondria integrity and elevated 8-OHdG expression in myocardial cells. Moreover, endosulfan increased the expressions of Fas, FasL, Caspase-8, Cleaved Caspase-8, Caspase-3 and Cleaved Caspase-3 in cardiac tissue. In vitro, human umbilical vein endothelial cells (HUVECs) were treated with different concentrations of endosulfan (1, 6 and 12μgmL-1) for 24h. An inhibitor for Ataxia Telangiectasia Mutated Protein (ATM) (Ku-55933, 10μM) was added in 12μgmL-1group for 2h before exposure to endosulfan. Results showed that endosulfan induced DNA damage and activated DNA damage response signaling pathway (ATM/Chk2 and ATR/Chk1) and consequent cell cycle checkpoint. Furthermore, endosulfan promoted the cell apoptosis through death receptor pathway resulting from oxidative stress. The results provide a new insight for mechanism of endosulfan-induced cardiovascular toxicity which will be helpful in future prevention of cardiovascular diseases induced by endosulfan.
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Jialiu
authors.initials: J
authors.lastname: Wei
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Lianshuang
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Lihua
authors.initials: L
authors.lastname: Ren
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Jianhui
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Junchao
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Yanbo
authors.initials: Y
authors.lastname: Li
authors.affiliation: National Research Centre for Environmental Toxicology (Entox), Queensland Alliance for Environmental Health Science (QAEHS), The University of Queensland, Coopers Plains, Brisbane, QLD 4108, Australia.
authors.forename: Cheng
authors.initials: C
authors.lastname: Peng
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China. Electronic address: xqzhou@ccmu.edu.cn.
authors.forename: Xianqing
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Toxicology and Hygienic Chemistry, School of Public Health, Capital Medical University, 100069 Beijing, China; Beijing Key Laboratory of Environmental Toxicology, Capital Medical University, Beijing 100069, China.
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Sun
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D004249:DNA Damage; D004726:Endosulfan / Q000009:adverse effects*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D018384:Oxidative Stress; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction
chemical_list: D051017:Apoptosis Regulatory Proteins; D004726:Endosulfan
keywords: DNA damage; DNA damage response; Endosulfan; HUVECs