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.

No abstract

No abstract

No abstract

HeLa S‐3 cells were treated with 195mPt‐radiolabeled cis‐diamminedichloroplatinum(II) (CDDP) under various conditions, and the relationship between lethal effect and the number of Pt atoms binding to DNA, RNA and proteins was examined. The mean lethal concentrations for the cells treated with CDDP at 37°C for 1, 2 and 3 h were 2.8, 2.0 and 1.1 μg/ml, respectively. By using identically treated cells, the number of Pt atoms combined with DNA, RNA and protein molecules were determined after fractionation of the cells using the method of Schneider. In this way, the Do values given as the drug concentration were substituted for the number of Pt atoms combined with each fraction, then the target volumes expressed as the reciprocals of Do values were calculated for each fraction. The results provide strong support for the idea that DNA is the primary target for cell killing by CDDP, and the target volumes were 5.17 × 104, 5.71 × 104 and 1.03 × 104 nucleotides for 1, 2 and 3 h treated cells, respectively.