The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease

J Invest Dermatol. 1999 Jul;113(1):26-31. doi: 10.1046/j.1523-1747.1999.00630.x.


Arsenic is widely distributed in nature in the form of either metalloids or chemical compounds, which cause a variety of pathologic conditions including cutaneous and visceral malignancies. Recently, reactive oxygen species have been hypothesized to be one of the causes of arsenic-induced carcinogenesis. 8-Hydroxy-2'-deoxyguanosine is one of the major reactive oxygen species-induced DNA base-modified products that is widely accepted as a sensitive marker of oxidative DNA damage. We studied the presence of 8-hydroxy-2'-deoxyguanosine by immunohistochemistry using N45.1 monoclonal antibody in 28 cases of arsenic-related skin neoplasms and arsenic keratosis as well as in 11 cases of arsenic-unrelated Bowen's diseases. The frequency of 8-hydroxy-2'-deoxyguanosine positive cases was significantly higher in arsenic-related skin neoplasms (22 of 28; 78%) than in arsenic-unrelated Bowen's disease (one of 11; 9%) (p < 0.001 by chi2 test). 8-Hydroxy-2'-deoxyguanosine was also detected in normal tissue adjacent to the arsenic-related Bowen's disease lesions. Furthermore, arsenic was detected by neutron activation analysis in the deparaffined skin tumor samples of arsenic-related disease (four of five; 80%), whereas arsenic was not detected in control samples. Our results strongly suggest the involvement of reactive oxygen species in arsenic-induced human skin cancer. Key word: neutron activation analysis.

MeSH terms

  • 8-Hydroxy-2'-Deoxyguanosine
  • Adult
  • Aged
  • Aged, 80 and over
  • Arsenic / adverse effects*
  • Arsenic / analysis
  • Bowen's Disease / chemically induced
  • Bowen's Disease / metabolism
  • Bowen's Disease / pathology
  • DNA Damage*
  • Deoxyguanosine / analogs & derivatives
  • Deoxyguanosine / analysis
  • Female
  • Humans
  • Immunohistochemistry
  • Male
  • Middle Aged
  • Neoplasms / chemically induced*
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neutron Activation Analysis
  • Oxidative Stress
  • Poisons / adverse effects*
  • Reactive Oxygen Species / physiology
  • Skin / chemistry
  • Skin / drug effects
  • Skin / pathology
  • Skin Neoplasms / chemically induced
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology


  • Poisons
  • Reactive Oxygen Species
  • 8-Hydroxy-2'-Deoxyguanosine
  • Deoxyguanosine
  • Arsenic