The Role of Oxidative DNA Damage in Human Arsenic Carcinogenesis: Detection of 8-Hydroxy-2′-Deoxyguanosine in Arsenic-Related Bowen's Disease

• Published in: Journal of investigative dermatology Vol. 113; no. 1; pp. 26 - 31
• Main Authors: Matsui, Miho, Nishigori, Chikako, Imamura, Sadao, Miyachi, Yoshiki, Toyokuni, Shinya, Takada, Jitsuya, Akaboshi, Mitsuhiko, Ishikawa, Manabu
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.07.1999; Nature Publishing
• Subjects: Adult; Aged; Aged, 80 and over; Arsenic - adverse effects; Arsenic - analysis; Biological and medical sciences; Bowen's Disease - chemically induced; Bowen's Disease - metabolism; Bowen's Disease - pathology; Deoxyguanosine - analogs & derivatives; Deoxyguanosine - analysis; Dermatology; DNA Damage; Female; Humans; Immunohistochemistry; Male; Medical sciences; 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; Tumors of the skin and soft tissue. Premalignant lesions; neutron activation analysis; Human; Dyskeratosis; Oxidative stress; Skin disease; Premalignant lesion; Arsenic; Pathogenesis; DNA; Skin; Bowen disease; Malignant tumor; Carcinogenesis
• ISSN: 0022-202X; 1523-1747
• 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 χ2 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.