Oxidative DNA damage is involved in ochratoxin A-induced G2 arrest through ataxia telangiectasia-mutated (ATM) pathways in human gastric epithelium GES-1 cells in vitro
Abstract
Ochratoxin A (OTA), one of the most abundant mycotoxin food contaminants, is classified as "possibly carcinogenic to humans." Our previous study showed that OTA could induce a G2 arrest in immortalized human gastric epithelium cells (GES-1). To explore the putative roles of oxidative DNA damage and the ataxia telangiectasia-mutated (ATM) pathways on the OTA-induced G2 arrest, the current study systematically evaluated the roles of reactive oxygen species (ROS) production, DNA damage, and ATM-dependent pathway activation on the OTA-induced G2 phase arrest in GES-1 cells. The results showed that OTA exposure elevated intracellular ROS production, which directly induced DNA damage and increased the levels of 8-OHdG and DNA double-strand breaks (DSBs). In addition, it was found that OTA treatment induced the phosphorylation of the ATM protein, as well as its downstream molecules Chk2 and p53, in response to DNA DSBs. Inhibition of ATM by the pharmacological inhibitor caffeine or siRNA effectively prevented the activation of ATM-dependent pathways and rescued the G2 arrest elicited by OTA. Finally, pretreatment with the antioxidant N-acetyl-L-cysteine (NAC) reduced the OTA-induced DNA DSBs, ATM phosphorylation, and G2 arrest. In conclusion, the results of this study suggested that OTA-induced oxidative DNA damage triggered the ATM-dependent pathways, which ultimately elicited a G2 arrest in GES-1 cells.
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Ochratoxin A induces oxidative DNA damage and triggers ATM-dependent G2 arrest in human gastric epithelium GES-1 cells.
“Ochratoxin A, one of the most abundant mycotoxin food contaminants, induces oxidative DNA damage and triggers an ATM-dependent G2 arrest in human gastric epithelium GES-1 cells [72].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [72]
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- Authors
- Cui, J., Liu, J., Wu, S., Wang, Y., Shen, H., Xing, L., Wang, J., Yan, X., & Zhang, X.
- Affiliations
- Hebei Medical University (CN)
- Corresponding author
- Zhang, Xianghong
- Venue
- Archives of Toxicology
- Published
- 2013-03-21
- Volume
- 87
- Issue
- 10
- Pages
- 1829-1840
- ISSN
- 0340-5761 (ISSN-L)
- 1432-0738
- OpenAlex
- W2091691492
- Cited by
- 33
- References
- 60
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2020: 6 · 2019: 5 · 2018: 1 · 2017: 2 · 2016: 1 · 2015: 6 · 2014: 3
- FWCI
- 4.02
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Archives of Toxicology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Mycotoxins in Agriculture and Food
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Keywords
- ochratoxin A, mycotoxins, oxidative DNA damage, G2 cell cycle arrest, reactive oxygen species, DNA double-strand breaks, 8-hydroxy-2'-deoxyguanosine, Chk2, p53, caffeine, N-acetylcysteine, gastric epithelial cells, GES-1 cells, DNA damage response
- MeSH terms
- Acetylcysteine, Antioxidants, Caffeine, Cell Line, DNA Damage, Gastric Mucosa, Humans, Ochratoxins, Phosphorylation, Reactive Oxygen Species, Oxidative Stress, RNA, Small Interfering, DNA Breaks, Double-Stranded, G2 Phase Cell Cycle Checkpoints, Ataxia Telangiectasia Mutated Proteins
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