The role of oxidative stress in citreoviridin-induced DNA damage in human liver-derived HepG2 cells.

TitleThe role of oxidative stress in citreoviridin-induced DNA damage in human liver-derived HepG2 cells.
Publication TypeJournal Article
Year of Publication2013
AuthorsBai Y, Jiang L-P, Liu X-F, Wang D, Yang G, Geng C-Y, Li Q, Zhong L-F, Sun Q, Chen M
JournalEnvironmental toxicology
Date Published2013 Dec 6
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. © 2013 Wiley Periodicals, Inc. Environ Toxicol, 2013.

DOI10.1155/2013/865181
Alternate JournalEnviron. Toxicol.