Arsenic induces oxidative DNA damage in mammalian cells
Abstract
Although arsenic is a well-established human carcinogen, the underlying carcinogenic mechanism(s) is not known. Using the human-hamster hybrid (A(L)) cell mutagenic assay that is sensitive in detecting mutagens that induce predominately multilocus deletions, we showed previously that arsenite is indeed a potent gene and chromosomal mutagen and that oxyradicals may be involved in the mutagenic process. In the present study, the effects of free radical scavenging enzymes on the cytotoxic and mutagenic potential of arsenic were examined using the AL cells. Concurrent treatment of cells with either superoxide dismutase or catalase reduced both the cytotoxicity and mutagenicity of arsenite by an average of 2-3 fold, respectively. Using immunoperoxidase staining with a monoclonal antibody specific for 8-hydroxy-2'-deoxyguanosine (8-OHdG), we demonstrated that arsenic induced oxidative DNA damage in A(L) cells. This induction was significantly reduced in the presence of the antioxidant enzymes. Furthermore, reducing the intracellular levels of non-protein sulfhydryls (mainly glutathione) using buthionine S-R-Sulfoximine increased the total mutant yield by more than 3-fold as well as the proportion of mutants with multilocus deletions. Taken together, our data provide clear evidence that reactive oxygen species play an important causal role in the genotoxicity of arsenic in mammalian cells.
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Chemotherapeutic agents can generate oxidative DNA damage; artesunate can induce 1,N6-ethenoadenine, single-strand breaks, and replication-associated double-strand breaks.
“Chem-otherapeutic agents can generate oxidative DNA damage. For example, artesunate can induce 1,N6-ethenoadenine, SSBs and replication-associated DSBs [23–25].”
From Functional interplay between ATM/ATR-mediated DNA damage response and DNA repair pathways in oxidative stress (2014) · cites this paper as [24]
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- Authors
- Kessel, M., Liu, S. X., Xu, A., Santella, R., & Hei, T. K.
- Affiliations
- Columbia University (US)
- Corresponding author
- Hei, Tom K.
- Venue
- Molecular and Cellular Biochemistry
- Published
- 2002-05
- Volume
- 234-235
- Issue
- 1
- Pages
- 301-308
- ISSN
- 0300-8177 (ISSN-L)
- 1573-4919
- OpenAlex
- W4243944514
- Cited by
- 135
- References
- 30
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 9 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 5 · 2014: 9 · 2013: 7 · 2012: 9
- FWCI
- 3.39
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Molecular and Cellular Biochemistry (publishedVersion)
- Funders
- U.S. Environmental Protection Agency
- National Institutes of Health
- National Institute of Environmental Health Sciences (P42 ES10349, ES 08821, P30-ES09089)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Physical Sciences › Environmental Science › Environmental Chemistry › Arsenic contamination and mitigation
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Heavy Metal Exposure and Toxicity
- Keywords
- arsenic, arsenite, oxidative DNA damage, genotoxicity, carcinogenesis, reactive oxygen species, superoxide dismutase, catalase, antioxidant enzymes, 8-hydroxy-2'-deoxyguanosine, glutathione, buthionine sulfoximine, cytotoxicity, mutagenicity
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