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Protective effect of N-acetylcysteine against DNA damage and S-phase arrest induced by ochratoxin A in human embryonic kidney cells (HEK-293)

Author:
Yang, Qian, Shi, Lei, Huang, Kunlun, Xu, Wentao
Source:
Food and chemical toxicology 2014 v.70 pp. 40-47
ISSN:
0278-6915
Subject:
DNA damage, acetylcysteine, antioxidants, cell cycle checkpoints, cyclin-dependent kinase, cyclins, hepatotoxicity, humans, immunotoxicity, kidney cells, membrane potential, mitochondrial membrane, nephrotoxicity, ochratoxin A, protective effect, superoxide dismutase, toxicology
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.
Agid:
5419382