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Cited by 537

The DOI matches its Crossref record; 58 of the 58 references it cites were found in a registry or an index.

Induction of oxyradicals by arsenic: Implication for mechanism of genotoxicity

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Liu, Su X., Athar, Mohammad, Lippai, Istvan, Waldren, Charles, Hei, Tom K.·2001·Proceedings of the National Academy of Sciences
DOI 10.1073/pnas.98.4.1643
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Abstract

Although arsenic is a well-established human carcinogen, the mechanisms by which it induces cancer remain poorly understood. We previously showed arsenite to be a potent mutagen in human–hamster hybrid (A L ) cells, and that it induces predominantly multilocus deletions. We show here by confocal scanning microscopy with the fluorescent probe 5′,6′-chloromethyl-2′,7′-dichlorodihydrofluorescein diacetate that arsenite induces, within 5 min after treatment, a dose-dependent increase of up to 3-fold in intracellular oxyradical production. Concurrent treatment of cells with arsenite and the radical scavenger DMSO reduced the fluorescent intensity to control levels. ESR spectroscopy with 4-hydroxy-2,2,6,6-tetramethyl-1-hydroxypiperidine (TEMPOL-H) as a probe in conjunction with superoxide dismutase and catalase to quench superoxide anions and hydrogen peroxide, respectively, indicates that arsenite increases the levels of superoxide-driven hydroxyl radicals in these cells. Furthermore, reducing the intracellular levels of nonprotein sulfhydryls (mainly glutathione) in A L cells with buthionine S-R-sulfoximine increases the mutagenic potential of arsenite by more than 5-fold. The data are consistent with our previous results with the radical scavenger DMSO, which reduced the mutagenicity of arsenic in these cells, and provide convincing evidence that reactive oxygen species, particularly hydroxyl radicals, play an important causal role in the genotoxicity of arsenical compounds in mammalian cells.

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Metadata

Authors
Liu, S. X., Athar, M., Lippai, I., Waldren, C., & Hei, T. K.
Venue
Proceedings of the National Academy of Sciences
Publisher
Proceedings of the National Academy of Sciences
Published
2001-02-06
Volume
98
Issue
4
Pages
1643-1648
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
DOI
10.1073/pnas.98.4.1643
OpenAlex
W2053658205
Cited by
537
References
58
FWCI
23.90
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Induction of oxyradicals by arsenic: Implication for mechanism of genotoxicity. https://app.cochat.ai/papers/10.1073/pnas.98.4.1643
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Liu, S. X., Athar, M., Lippai, I., Waldren, C., & Hei, T. K. (2001). Induction of oxyradicals by arsenic: Implication for mechanism of genotoxicity. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.98.4.1643

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