Induction of germline cell cycle arrest and apoptosis by sodium arsenite in Caenorhabditis elegans.
Induction of germline cell cycle arrest and apoptosis by sodium arsenite in Caenorhabditis elegans.
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DOI：
10.1021/tx0601962
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发表时间：
2007-01
影响因子：
4.1
通讯作者：
Shunchang Wang;Ye Zhao;Lijun Wu;Mingli Tang;C. Su;T. Hei;Zengliang Yu
中科院分区：
文献类型：
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作者：
Shunchang Wang;Ye Zhao;Lijun Wu;Mingli Tang;C. Su;T. Hei;Zengliang Yu
秀丽隐杆线虫已被证明是研究水生毒性的模式生物。尽管流行病学研究表明，砷对人类具有致畸和致癌作用，但致命性试验表明，秀丽隐杆线虫对无机砷的敏感性低于迄今已测试过的任何其他生物体。在本研究中，我们使用更具延展性的秀丽隐杆线虫生殖系作为体内系统来研究亚砷酸盐的遗传毒性效应。动物暴露于浓度为1 μ m ~ 0.5 mM的亚砷酸钠后，分别用DAPI染色和吖啶橙活体染色对有丝分裂生殖细胞和种系凋亡进行评分。在DMSO（0.1%）存在下，将秀丽隐杆线虫暴露于0.01 mM亚砷酸盐中24 h，采用CM-H(2)DCFDA生命染色法半定量活性氧（ROS）。结果表明，砷暴露使秀丽隐杆线虫幼虫数量减少，有丝分裂细胞周期阻滞和种系凋亡，并在一定程度上表现出浓度依赖性和时间依赖性。添加0.1% DMSO完全恢复砷诱导的细胞周期阻滞，部分抑制种系凋亡。此外，剂量为0.01 mM的亚砷酸盐显著增加了动物肠道中ROS的产生，而DMSO处理可以降低这一水平。本研究还提示秀丽隐杆线虫可作为研究砷致遗传毒性作用机制的体内模型系统。
The nematode Caenorhabditis elegans has been shown to be a model organism in studying aquatic toxicity. Although epidemiological studies have shown that arsenic is teratogenic and carcinogenic to humans, the lethality assay indicated that C. elegans is less sensitive to inorganic arsenic than any other organisms that have been tested thus far. In the present study, we used the more malleable germline of C. elegans as an in vivo system to investigate the genotoxic effects of arsenite. After animals were exposed to sodium arsenite at concentrations ranging from 1 microM to 0.5 mM, mitotic germ cells and germline apoptosis were scored after DAPI staining and acridine orange vital staining, respectively. DMSO rescue experiments were performed by exposing C. elegans to 0.01 mM arsenite in the presence of DMSO (0.1%) for 24 h, and reactive oxygen species (ROS) were semiquantified by CM-H(2)DCFDA vital staining. The results indicated that arsenic exposure reduced the brood size of C. elegans and caused mitotic cell cycle arrest and germline apoptosis, which, to some extent, exhibited a concentration- and time-dependent manner. The addition of 0.1% DMSO completely rescued arsenic-induced cell cycle arrest and partially suppressed germline apoptosis. Furthermore, treatment of animals with arsenite at a dose of 0.01 mM significantly increased ROS production in the intestine, which could be reduced by DMSO treatment. The present study also indicated that C. elegans might be used as an in vivo model system to study the mechanisms of arsenic-induced genotoxic effects.