Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells
Arsenite inhibits mitotic division and perturbs spindle dynamics in HeLa S3 cells
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DOI：
10.1093/carcin/19.5.889
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发表时间：
1998-05-01
期刊：
影响因子：
4.7
通讯作者：
Lee, TC
中科院分区：
文献类型：
--
作者：
Huang, SC;Lee, TC
砷化合物是已知的人类致癌物质，已被证明可以干扰细胞周期进程，并在各种细胞系统中诱导细胞遗传学改变。我们在这里报告了亚砷酸盐处理24小时诱导人类细胞系有丝分裂的积累。HeLa S3和KB细胞最敏感，5mU亚砷酸钠处理HeLa S3细胞后，35%的细胞停滞于有丝分裂期，KB细胞经10mU亚砷酸钠处理后，35%的细胞停滞在有丝分裂期。在显微镜下，我们观察到有丝分裂细胞的异常分裂形态，包括染色体错乱聚集，有丝分裂纺锤体的极距延长，微管免疫荧光增强。有丝分裂细胞的纺锤体微管对诺康唑诱导的溶解有更强的抵抗力，有丝分裂细胞的纺锤体微管比对照细胞更耐受。根据浊度分析，浓度低于100 mU M的亚砷酸盐显著促进了微管蛋白的聚合，因为纺锤体动力学在有丝分裂过程中起着至关重要的作用，我们的结果表明亚砷酸盐诱导的有丝分裂停滞可能是由于亚砷酸盐对纺锤体动力学的减弱所致。
Arsenical compounds, known to be human carcinogens, were shown to disturb cell cycle progression and induce cytogenetic alterations in a variety of cell systems. We report here that a 24 h treatment of arsenite induced mitotic accumulation in human cell lines. HeLa S3 and KB cells were most susceptible: 35% of the total cell population was arrested at the mitotic stage after treatment with 5 mu M sodium arsenite in HeLa S3 cells and after 10 mu M in KB cells. Under a microscope, we observed abnormal mitotic figures in arsenite-arrested mitotic cells, including deranged chromosome congression, elongated polar distance of mitotic spindle, and enhanced microtubule immunofluorescence. The spindle microtubules of arsenite-arrested mitotic cells were more resistant to nocodazole-induced dissolution than those of control mitotic cells. According to turbidity assay, arsenite at concentrations below 100 mu M significantly enhanced polymerization of tubulins, Since spindle dynamics play a crucial role in mitotic progression, our results suggest that arsenite-induced mitotic arrest may be due to arsenite's effects on attenuation of spindle dynamics.