title: The role of oxidative stress in citreoviridin-induced DNA damage in human liver-derived HepG2 cells.
abstract: We hypothesize that citreoviridin (CIT) induces DNA damage in human liver-derived HepG2 cells through an oxidative stress mechanism and that N-acetyl-l-cysteine (NAC) protects against CIT-induced DNA damage in HepG2 cells. CIT-induced DNA damage in HepG2 cells was evaluated by alkaline single-cell gel electrophoresis assay. To elucidate the genotoxicity mechanisms, the level of oxidative DNA damage was tested by immunoperoxidase staining for 8-hydroxydeoxyguanosine (8-OHdG); the intracellular generation of reactive oxygen species (ROS) and reduced glutathione (GSH) were examined; mitochondrial membrane potential and lysosomal membranes' permeability were detected; furthermore, protective effects of NAC on CIT-induced ROS formation and CIT-induced DNA damage were evaluated in HepG2 cells. A significant dose-dependent increment in DNA migration was observed at tested concentrations (2.50-10.00 µM) of CIT. The levels of ROS, 8-OHdG formation were increased by CIT, and significant depletion of GSH in HepG2 cells was induced by CIT. Destabilization of lysosome and mitochondria was also observed in cells treated with CIT. In addition, NAC significantly decreased CIT-induced ROS formation and CIT-induced DNA damage in HepG2 cells. The data indicate that CIT induces DNA damage in HepG2 cells, most likely through oxidative stress mechanisms; that NAC protects against DNA damage induced by CIT in HepG2 cells; and that depolarization of mitochondria and lysosomal protease leakage may play a role in CIT-induced DNA damage in HepG2 cells.
authors: Division of Environmental Health Sciences, College of Public Health, The Ohio State University, Columbus, Ohio, USA; Department of Food Nutrition and Safety, Dalian Medical University, No. 9, West Segment of South Lvshun Road, Dalian, 116044, Liaoning, China.
authors: Yuntao
authors: Y
authors: Bai
authors: Li-Ping
authors: LP
authors: Jiang
authors: Xiao-Fang
authors: XF
authors: Liu
authors: Dong
authors: D
authors: Wang
authors: Guang
authors: G
authors: Yang
authors: Cheng-Yan
authors: CY
authors: Geng
authors: Qiujuan
authors: Q
authors: Li
authors: Lai-Fu
authors: LF
authors: Zhong
authors: Qinghua
authors: Q
authors: Sun
authors: Min
authors: M
authors: Chen
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000111:Acetylcysteine / Q000494:pharmacology; D001313:Aurovertins / Q000633:toxicity*; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives; D005978:Glutathione / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008247:Lysosomes / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D009183:Mycotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D001313:Aurovertins; D009183:Mycotoxins; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D005978:Glutathione; C014416:citreoviridin; D000111:Acetylcysteine
keywords: 8-OHdG; CIT; GSH; HepG2 cells; ROS; single-cell gel electrophoresis assay