Arsenic induces oxidative DNA damage in mammalian cells

  • Maris Kessel
  • Su Xian Liu
  • An Xu
  • Regina Santella
  • Tom K. Heil
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 37)


Although arsenic is a well-established human carcinogen, the underlying carcinogenic mechanism(s) is not known. Using the human-hamster hybrid (AL) 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 ALcells. Concurrent treatment of cells with either superoxide dis-mutase 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 ALcells. This induction was significantly reduced in the presence of the antioxidant enzymes. Furthermore, reducing the intracellular levels of non-protein sulthydryls (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. (Mol Cell Biochem 234/235: 301-308, 2002)

Key words

arsenic mutagenicity oxidative stress antioxidant enzymes 8-OHdG 


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Copyright information

© Springer Science+Business Media New York 2002

Authors and Affiliations

  • Maris Kessel
    • 1
  • Su Xian Liu
    • 1
  • An Xu
    • 1
  • Regina Santella
    • 2
  • Tom K. Heil
    • 1
  1. 1.College of Physicians and SurgeonsCenter for Radiological ResearchUSA
  2. 2.Columbia UniversityDepartment of Environmental Health Sciences, Joseph Mailman School of Public HealthUSA

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