Chronic low dose arsenic exposure preferentially perturbs mitotic phase of the cell cycle.

Q2 Biochemistry, Genetics and Molecular Biology
Suthakar Ganapathy, Jian Liu, Rui Xiong, Tianqi Yu, Alexandros Makriyannis, Changyan Chen
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引用次数: 10

Abstract

Environmental pollution is a big challenge for human survival. Arsenic compounds are well-known biohazard, the exposure of which is closely linked to onsets of various human diseases, particularly cancers. Upon chronically exposing to arsenic compounds, genomic integrity is often disrupted, leading to tumor development. However, the underlying mechanisms by which chronic, low dose arsenic exposure targets genetic stability to initiate carcinogenesis still remain not fully understood. In this study, human lung epithelial BEAS-2B cells and keratinocytes were treated with 0.5 μM of sodium arsenite for one month (designated as BEAS-2B-SA cells or keratinocytes-SA), and its effect on cell cycle responses was analyzed. After being arrested in mitotic phase of the cell cycle by nocodazole treatment, BEAS-2B-SA cells or keratinocytes-SA were delayed to enter next cytokinesis. The lagging exit of the cells from mitosis was accompanied by a sustained Plk1 phosphorylation, which led to a persistent activation of the mitotic regulators BubR1 and Cdc27. As the result, cyclin B1 (clnB1) degradation was attenuated. BEAS-2B-SA cells or keratinocytes-SA also expressed a constitutively active Akt. The cytogenetic analysis showed an increased numbers of aneuploidy in these cells. The suppression of Akt reversed the aberrant expressions of the mitotic regulators, delay of mitotic exit as well as chromosomal aberrations. Our findings suggest that a long-term exposure to low dose sodium arsenite aberrantly retains the catenation of mitosis, which facilitates establishing genetic instability and predisposes the cells to tumorigenesis.

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慢性低剂量砷暴露优先扰乱细胞周期的有丝分裂期。
环境污染是人类生存面临的巨大挑战。砷化合物是众所周知的生物危害,接触砷与各种人类疾病,特别是癌症的发病密切相关。在长期暴露于砷化合物后,基因组完整性经常被破坏,导致肿瘤的发展。然而,慢性低剂量砷暴露以遗传稳定性为目标引发致癌的潜在机制仍未完全了解。本研究采用0.5 μM亚砷酸钠处理人肺上皮BEAS-2B细胞和角质形成细胞1个月(分别称为BEAS-2B- sa细胞或角化细胞- sa),分析其对细胞周期反应的影响。经诺可达唑处理后,BEAS-2B-SA细胞或角化细胞- sa被阻滞在细胞周期的有丝分裂期,延迟进入下一个细胞分裂期。细胞有丝分裂的滞后退出伴随着持续的Plk1磷酸化,这导致有丝分裂调节因子BubR1和Cdc27的持续激活。结果,细胞周期蛋白B1 (clnB1)降解减弱。BEAS-2B-SA细胞或角化细胞- sa也表达构成型活性Akt。细胞遗传学分析显示,这些细胞的非整倍体数量增加。Akt的抑制逆转了有丝分裂调控因子的异常表达、有丝分裂退出延迟以及染色体畸变。我们的研究结果表明,长期暴露于低剂量亚砷酸钠会异常地保留有丝分裂的链状链,这有助于建立遗传不稳定性并使细胞容易发生肿瘤。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes and Cancer
Genes and Cancer Biochemistry, Genetics and Molecular Biology-Genetics
CiteScore
3.90
自引率
0.00%
发文量
6
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