Arsenic Trioxide Co-exposure Potentiates Benzo(a)pyrene Genotoxicity by Enhancing the Oxidative Stress in Human Lung Adenocarcinoma Cell
Arsenic Trioxide Co-exposure Potentiates Benzo(a)pyrene Genotoxicity by Enhancing the Oxidative Stress in Human Lung Adenocarcinoma Cell
复制标题
三氧化二砷共暴露通过增强人肺腺癌细胞的氧化应激来增强苯并(a)芘的基因毒性
DOI：
10.1007/s12011-013-9819-0
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发表时间：
2013-12-01
影响因子：
3.9
通讯作者：
Zhang, Zunzhen
中科院分区：
文献类型：
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作者：
Chen, Chengzhi;Jiang, Xuejun;Zhang, Zunzhen
虽然三氧化二砷（As 2 O3）和苯并（a）芘（BaP）都是公认的人类致癌物，但As 2 O3和BaP之间的相互作用是协同还是拮抗，目前的研究还存在争议。此外，造成综合效应的机制仍不清楚。在本研究中，我们研究了As 2 O3（1，5，10 μM）和BaP（5，10，20 μM）在培养的A549细胞中的潜在相互作用，通过单独或联合使用不同浓度的BaP和As 2 O3 24 h。采用四氮唑（3-（4，5-二甲基噻唑-2-基）-2，5-二苯基溴化四氮唑）染料比色法、集落形成试验、荧光探针法、化学比色法、彗星试验和微核试验，研究了As 2 O3和BaP单独和联合作用对细胞毒性、DNA/染色体损伤和氧化应激的影响。我们的研究结果表明，As 2 O3协同增强BaP诱导的细胞毒性，遗传毒性和氧化应激水平在不同的测试浓度。不同浓度的BaP均能增加细胞内谷胱甘肽（GSH）含量，但单独或与As_2O_3共处理均能显著降低细胞内GSH含量。总而言之，我们的研究结果表明，As 2 O3可能主要通过升高细胞内活性氧自由基、降低GSH含量和超氧化物歧化酶活性，从而促进高水平的氧化应激，从而与BaP发挥协同的细胞毒性和遗传毒性作用，这可能是As 2 O3协同致癌作用的关键机制。
Although both arsenic trioxide (As2O3) and benzo(a)pyrene (BaP) are well-established human carcinogens, the interaction between As2O3and BaP is synergistic or antagonistic remains controversial in terms of the existing studies. In addition, the mechanisms responsible for the combined effects are still unclear. In this study, we examined the potential interactive effects between As2O3(1, 5, and 10 μM) and BaP (5, 10, and 20 μM) in cultured A549 cells by treating with BaP and As2O3alone or in combination at various concentrations for 24 h. The single and combined effects of As2O3and BaP on the cytotoxicity, DNA/chromosomal damage, and oxidative stress were examined by using tetrazolium (3-(4,5-dimethyithiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) dye colorimetric assay, colony formation assay, fluorescence probe, chemical colorimetry, comet assay as well as micronucleus test. Our results showed that As2O3synergistically enhanced the cytotoxicity, genotoxicity, and level of oxidative stress induced by BaP at various tested concentrations. Also, our experimental results showed that intracellular glutathione (GSH) contents were increased by various doses of BaP, but single or cotreatment with As2O3significantly decreased the GSH level in the cells at all tested concentrations. Taken together, our results suggest that As2O3may exert its synergistic cyto- and genotoxic effects with BaP mainly via elevated intracellular reactive oxygen species and reduced GSH contents and superoxide dismutase activities, thus promoting high level of oxidative stress, which may be a pivotal mechanism underlying As2O3cocarcinogenic action.