title: Protective effect of N-acetylcysteine against DNA damage and S-phase arrest induced by ochratoxin A in human embryonic kidney cells (HEK-293).
abstract: N-acetylcysteine (NAC) has recently gained particular interest as a beneficial antioxidant. This study investigated the protective effects of NAC against ochratoxin A (OTA)-induced DNA damage and S-phase arrest in human embryonic kidney cells (HEK-293). OTA exposure results in nephrotoxicity, hepatotoxicity as well as immunotoxicity; and, in the present study, the toxicity of OTA toward HEK-293 cells was explored by analyzing the involvement of the oxidative pathway. It was found that OTA treatment led to oxidative damage; meanwhile, OTA treatment induced significant DNA damage and S-phase arrest by down-regulating cyclin A2, cyclin E1, and CDK2 expression. However, NAC pretreatment alleviated OTA-induced ROS overproduction, the loss of mitochondrial membrane potential (ΔΨm), and the decrease in superoxide dismutase (SOD) activity. NAC pretreatment was also discovered to attenuate OTA-induced DNA damage using the comet assay and by determining the expression of γ-H2AX. In addition, NAC pretreatment partly ameliorated OTA-induced S-phase arrest by preventing the down-regulation of cyclin A2, cyclin E1 and CDK2 expression in HEK-293 cells. All of these results demonstrated that oxidative damage was involved in OTA-induced DNA damage and cell cycle arrest in HEK-293 cells. Therefore, NAC has the potential to reverse the DNA damage and S-phase arrest induced by OTA.
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Shi
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China; The Supervision, Inspection & Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, PR China.
authors.forename: Kunlun
authors.initials: K
authors.lastname: Huang
authors.affiliation: Laboratory of Food Safety and Molecular Biology, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, PR China; The Supervision, Inspection & Testing Center of Genetically Modified Organisms, Ministry of Agriculture, Beijing 100083, PR China. Electronic address: xuwentaoboy@sina.com.
authors.forename: Wentao
authors.initials: W
authors.lastname: Xu
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D020552:Comet Assay; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D051357:Cyclin-Dependent Kinase 2 / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage / Q000187:drug effects*; D015536:Down-Regulation; D057809:HEK293 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009793:Ochratoxins / Q000633:toxicity*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
chemical_list: D000975:Antioxidants; C503721:CCNA2 protein, human; C475820:CCNE1 protein, human; D056751:Cyclin A2; D019927:Cyclin E; D009793:Ochratoxins; D015513:Oncogene Proteins; D017382:Reactive Oxygen Species; C025589:ochratoxin A; D013482:Superoxide Dismutase; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2; D000111:Acetylcysteine
keywords: Cell cycle arrest; DNA damage; HEK-293 cells; N-acetylcysteine; Ochratoxin A