Arsenic induces DNA damage via reactive oxygen species in human cells
D Li1, K Morimoto, T Takeshita
1Department of Preventive Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka.
Abstract:
To elucidate arsenic-induced oxidative DNA damage, the genotoxicity of arsenic in human cells was comparatively studied with single cell gel electrophoresis (SCGE) assay in combination with the observation of the protective effects of dimethyl sulfoxide (DMSO) and catalase. Arsenic, at the concentration of 2.4 μM by coincubation for 24 hours, significantly induced DNA damage in HL60, a human promyelocytic leukemia cell line. In contrast, significant DNA damage was found in human mononucleocytes at the concentration of 4.8 μM or above. The cells were incubated separately with DMSO (12 mM/l), a well-known hydroxyl radical (OH(-)) scavenger, and catalase (1,300 U/ml), a hydrogen peroxide (H(2)O(2)) scavenger, for 6 hours and then further coincubated with various concentrations of arsenic for 24 hours at 37°C and 5% CO(2). The findings showed that both DMSO and catalase significantly reduced the arsenic-induced tail moment, a parameter of total damaged DNA, in HL60 and mononucleocytes. Hence our findings indicate that arsenic, with micromolar concentrations, induces typical and various extents of DNA damage in human cells via reactive oxygen species in a dose-dependent manner.
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