Acetoaminophen-induced accumulation of 8-oxodeoxyguanosine through reduction of Ogg1 DNA repair enzyme in C6 glioma cells
Open accessAbstract
Large doses of acetaminophen (APAP) could cause oxidative stress and tissue damage through production of reactive oxygen/nitrogen (ROS/RNS) species and quinone metabolites of APAP. Although ROS/RNS are known to modify DNA, the effect of APAP on DNA modifications has not been studied systematically. In this study, we investigate whether large doses of APAP can modify the nuclear DNA in C6 glioma cells used as a model system, because these cells contain cytochrome p450-related enzymes responsible for APAP metabolism and subsequent toxicity (Geng and Strobel, 1995). Our results revealed that APAP produced ROS and significantly elevated the 8-oxo- deoxyguanosine (8-oxodG) levels in the nucleus of C6 glioma cells in a time and concentration dependent manner. APAP significantly reduced the 8- oxodG incision activity in the nucleus by decreasing the activity and content of a DNA repair enzyme, Ogg1. These results indicate that APAP in large doses can increase the 8-oxodG level partly through significant reduction of Ogg1 DNA repair enzyme.
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Mitochondrial DNA is extremely sensitive to oxidative/nitrative damage due to its location closer to the inner mitochondrial membrane, relatively low amounts of histone, anti-oxidant enzymes and mtGSH, and low levels of polyamines and DNA repair enzymes.
“Indeed, mitochondrial DNA is extremely sensitive to oxidative/nitrative damage due to (A) its location closer to the inner mitochondrial membrane; (B) the relatively low amount of histone, anti-oxidant enzymes, and mtGSH, and (C) the low levels of polyamines and DNA repair enzymes [78], [79].”
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References 33 · Cited by 32
Research works printed but not linked: 10
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- Authors
- Wan, J., Bae, M.-A., & Song, B.-J.
- Affiliations
- National Institutes of Health (US)
- ORCID
- Song, Byoung-Joon
- Venue
- Experimental & Molecular Medicine
- Published
- 2004-02-01
- Volume
- 36
- Issue
- 1
- Pages
- 71-77
- ISSN
- 1226-3613 (ISSN-L)
- 2092-6413
- OpenAlex
- W2084223682
- Cited by
- 32
- References
- 33
- Citations by year
- 2022: 1 · 2021: 2 · 2019: 1 · 2018: 1 · 2017: 2 · 2015: 2 · 2014: 4 · 2013: 3
- FWCI
- 1.39
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Experimental & Molecular Medicine (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Topics
- 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
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Drug-Induced Hepatotoxicity and Protection
- Keywords
- paracetamol, 8-hydroxy-2'-deoxyguanosine, OGG1, DNA repair, oxidative DNA damage, reactive oxygen species, C6 glioma cells, cytochrome P450, drug toxicity, quinone metabolites
- MeSH terms
- Acetaminophen, Animals, Deoxyguanosine, DNA, DNA Damage, DNA Repair, Glioma, Glutathione, Humans, Reactive Oxygen Species, Analgesics, Non-Narcotic, Reactive Nitrogen Species, DNA Glycosylases, Cell Line, Tumor, Rats
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