Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: An implication for the paradoxical mechanism
Sodium arsenite and arsenic trioxide differently affect the oxidative stress, genotoxicity and apoptosis in A549 cells: An implication for the paradoxical mechanism
复制标题
亚砷酸钠和三氧化二砷对 A549 细胞的氧化应激、基因毒性和细胞凋亡有不同的影响：矛盾机制的暗示
DOI：
10.1016/j.etap.2013.08.002
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发表时间：
2013-11-01
影响因子：
4.3
通讯作者：
Zhang, Zunzhen
中科院分区：
文献类型：
--
作者：
Jiang, Xuejun;Chen, Chengzhi;Zhang, Zunzhen
虽然砷的毒性在很大程度上依赖于其化学形态，但很少有研究考虑到亚砷酸钠(NaAsO2)是一种强大的致癌物，而三氧化二砷(As2O)是一种有效的治疗剂这一矛盾现象。本研究比较了NaAsO_2和As_2O_3对人肺腺癌A549细胞的细胞活力、克隆形成、细胞周期进程、细胞凋亡、遗传毒性和氧化应激的影响。结果表明，NaAsO_2和As_2O_3均可引起细胞氧化应激、遗传毒性、细胞毒性、细胞周期停滞和细胞凋亡，而As_2O_3诱导细胞产生更多的活性氧(ROS)，其中超氧化物歧化酶(SOD)活性和细胞内谷胱甘肽(GSH)水平较NaAsO_2显著降低。此外，As_2O_3处理的细胞DNA损伤、染色体断裂、细胞周期停滞和细胞凋亡的程度比NaAsO_2处理的细胞更严重。这些结果提示，AsO_2和As_2O_3的不同作用和机制可能是砷在致癌和抗癌作用中的矛盾作用的原因。(C)2013爱思唯尔B.V.保留所有权利。
Although arsenic toxicity greatly depends on its chemical forms, few studies have taken into account the paradoxical phenomenon which is manifested by that sodium arsenite (NaAsO2) acts as a potent carcinogen but arsenic trioxide (As2O3) serves as an effective therapeutic agent. In this study, we compared the in vitro effects of NaAsO2 and As2O3 on cell viability, colony formation, cell cycle progression, apoptosis, genotoxicity and oxidative stress in human lung adenocarcinoma A549 cells. Our results demonstrated that both NaAsO2 and As2O3 caused oxidative stress, genotoxicity, cytotoxicity, cell cycle arrest as well as apoptosis, while As2O3 induced higher production of reactive oxygen species (ROS) with a more remarkable decrease in superoxide dismutase (SOD) activities and intracellular levels of glutathione (GSH) than NaAsO2. Moreover, the degree of DNA damage, chromosomal breakage, cell cycle arrest and apoptosis in As2O3-treated cells were more severe than those in NaAsO2-treated cells. These findings suggest that differential effects and mechanisms of NaAsO2 and As2O3 may responsible for the paradoxical effects of arsenic on the carcinogenesis and anticancer function. (C) 2013 Elsevier B.V. All rights reserved.