Arsenite causes DNA damage in keratinocytes via generation of hydroxyl radicals

Honglian Shi, Laurie G. Hudson, Wei Ding, Suwei Wang, Karen L. Cooper, Shimin Liu, Yan Chen, Xianglin Shi, Ke Jian Liu

Research output: Contribution to journalArticlepeer-review

134 Scopus citations


Arsenic is an environmental and occupational toxin. Dermatologic toxicities due to arsenic exposure are well-documented and include basal cell and squamous cell carcinomas. However, the mechanism of arsenic-induced skin cancer is not well-understood. Recent studies indicate that arsenic exposure results in the generation of reactive oxygen species (ROS) and oxidative stress. Here, we examined the chemical nature of the specific ROS, studied the interrelationship among these species, and identified the specific species that is responsible for the subsequent DNA damage in a spontaneously immortalized keratinocyte cell line. We detected the formation of O2.- and H 2O2 in keratinocytes incubated with arsenite [As(III)] but not with arsenate. As(III)-induced DNA damage was detected in a concentration-dependent manner and evident at low micromolar concentrations. Catalase, an H2O2 scavenger, eliminated H 2O2 and reduced the As(III)-mediated DNA damage. Superoxide dismutase, by enhancing the production of H2O2 and .OH, significantly increased the As(III)-mediated DNA damage. Sodium formate, a competitive scavenger for .OH, and deferoxamine, a metal chelator, both reduced the DNA damage. These results suggest that exposure to arsenite generates O2.- and H2O 2, and .OH, derived from H2O2, is responsible, at least in part, for the observed DNA damage. These findings demonstrate arsenic-induced formation of specific ROS and provide the direct evidence of .OH-mediated DNA damage in keratinocytes, which may play an important role in the mechanism for arsenic-induced skin carcinogenicity.

Original languageEnglish
Pages (from-to)871-878
Number of pages8
JournalChemical Research in Toxicology
Issue number7
StatePublished - Jul 2004

ASJC Scopus subject areas

  • Toxicology


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