The role of oxidative DNA damage in human arsenic carcinogenesis: detection of 8-hydroxy-2'-deoxyguanosine in arsenic-related Bowen's disease.
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.
Department of Dermatology, Graduate School of Medicine, Kyoto University, Japan.
M
M
Matsui
C
C
Nishigori
S
S
Toyokuni
J
J
Takada
M
M
Akaboshi
M
M
Ishikawa
S
S
Imamura
Y
Y
Miyachi
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001151:Arsenic / Q000009:adverse effects* / Q000032:analysis; D001913:Bowen's Disease / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D004249:DNA Damage; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D009501:Neutron Activation Analysis; D018384:Oxidative Stress; D011042:Poisons / Q000009:adverse effects*; D017382:Reactive Oxygen Species / Q000502:physiology; D012867:Skin / Q000737:chemistry / Q000187:drug effects / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology
D011042:Poisons; D017382:Reactive Oxygen Species; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D001151:Arsenic