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砷通过活性氧物质在人体细胞中诱导 DNA 损伤。

Arsenic induces DNA damage via reactive oxygen species in human cells.

机构信息

Department of Preventive Medicine, Osaka University Graduate School of Medicine, 2-2 Yamada-oka, Suita, Osaka.

出版信息

Environ Health Prev Med. 2001 Apr;6(1):27-32. doi: 10.1007/BF02897306.

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.

摘要

为了阐明砷诱导的氧化 DNA 损伤,我们比较研究了单细胞凝胶电泳(SCGE)测定法与二甲基亚砜(DMSO)和过氧化氢酶观察相结合,研究了砷对人细胞的遗传毒性。在共孵育 24 小时的情况下,浓度为 2.4 μM 的砷显著诱导 HL60(人早幼粒细胞白血病细胞系)中的 DNA 损伤。相比之下,在浓度为 4.8 μM 或更高时,人单核细胞中发现了明显的 DNA 损伤。将细胞分别用二甲基亚砜(12 mM/l),一种已知的羟自由基(OH(-))清除剂和过氧化氢酶(1,300 U/ml),一种过氧化氢(H(2)O(2))清除剂,孵育 6 小时,然后在 37°C 和 5%CO(2)下进一步与不同浓度的砷共孵育 24 小时。结果表明,二甲基亚砜和过氧化氢酶均显著降低了 HL60 和单核细胞中砷诱导的尾矩(总损伤 DNA 的参数)。因此,我们的研究结果表明,砷以微摩尔浓度通过活性氧物种以剂量依赖的方式诱导人细胞中典型的和不同程度的 DNA 损伤。

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