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三氧化二砷在人 Jurkat T 淋巴瘤细胞中的遗传毒性机制

GENOTOXIC MECHANISMS OF ARSENIC TRIOXIDE IN HUMAN JURKAT T-LYMPHOMA CELLS.

作者信息

Yedjou Clement, Sutton La'mont, Tchounwou Paul

机构信息

Cellomics and Toxicogenomics Research Laboratory, NIH-Center for Environmental Health, College of Science, Engineering and Technology, Jackson State University, 1400 Lynch Street, P.O. Box 18540, Jackson, Mississippi, USA.

出版信息

Met Ions Biol Med. 2008;10:495-499.

Abstract

Arsenic trioxide (As(2)O(3)) has cytotoxic effects on several cancer cell lines. However, the molecular mechanisms of action remain to be elucidated. Hence, the aim of the present study was to evaluate the cytotoxicity and genotoxicity induced by As(2)O(3) in a human Jurkat T-lymphoma cell line using the trypan blue exclusion test and alkaline single cell gel electrophoresis (Comet) assays, respectively. Jurkat T-cells were treated with different doses of As(2)O(3) for 24 and 48 h prior to cytogenetic assessment. Data obtained from the trypan blue exclusion test indicated that As(2)O(3) significantly (p < 0.05) reduced the viability of Jurkat T-cells in a dose and time-dependent manner. Data generated from the comet assay also indicated a significant dose and time-dependent increase in DNA damage in Jurkat T-cells associated with As(2)O(3) exposure. We observed a significant increase (P < 0.05) in comet tail-length, tail arm and tail moment, as well as in percentages of DNA cleavage at all doses tested, showing an evidence As(2)O(3) -induced genotoxic damage in Jurkat T-cells. This study confirms that the comet assay is a sensitive and effective method to detect DNA damage caused by heavy metals such as arsenic. Taken together, our findings suggest that As(2)O(3) exposure significantly (p < 0.05) reduces cellular viability and induces DNA damage in human Jurkat T-lymphoma cells.

摘要

三氧化二砷(As₂O₃)对多种癌细胞系具有细胞毒性作用。然而,其分子作用机制仍有待阐明。因此,本研究的目的是分别使用台盼蓝排斥试验和碱性单细胞凝胶电泳(彗星试验)评估As₂O₃在人Jurkat T淋巴瘤细胞系中诱导的细胞毒性和遗传毒性。在进行细胞遗传学评估之前,将Jurkat T细胞用不同剂量的As₂O₃处理24小时和48小时。从台盼蓝排斥试验获得的数据表明,As₂O₃以剂量和时间依赖性方式显著(p < 0.05)降低了Jurkat T细胞的活力。彗星试验产生的数据还表明,与As₂O₃暴露相关的Jurkat T细胞中的DNA损伤存在显著的剂量和时间依赖性增加。我们观察到在所有测试剂量下,彗星尾长、尾臂和尾矩以及DNA裂解百分比均显著增加(P < 0.05),表明有证据表明As₂O₃在Jurkat T细胞中诱导了遗传毒性损伤。本研究证实彗星试验是检测由砷等重金属引起的DNA损伤的一种灵敏且有效的方法。综上所述,我们的研究结果表明,As₂O₃暴露显著(p < 0.05)降低了人Jurkat T淋巴瘤细胞的细胞活力并诱导了DNA损伤。

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