Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells
Lasting DNA Damage and Aberrant DNA Repair Gene Expression Profile Are Associated with Post-Chronic Cadmium Exposure in Human Bronchial Epithelial Cells
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持久的 DNA 损伤和异常的 DNA 修复基因表达谱与人支气管上皮细胞慢性镉暴露有关
DOI：
10.3390/cells8080842
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发表时间：
2019-08
期刊：
影响因子：
6
通讯作者：
Lau Andy T. Y.
中科院分区：
文献类型：
--
作者：
Tan Heng Wee;Liang Zhan-Ling;Yao Yue;Wu Dan-Dan;Mo Hai-Ying;Gu Jiang;Chiu Jen-Fu;Xu Yan-Ming;Lau Andy T. Y.
镉是一种广泛存在的环境污染物和致癌物。虽然Cd诱导致癌的确切机制尚不清楚，但先前的急性/慢性Cd暴露研究表明，Cd通过多种机制发挥其细胞毒性和致癌作用，包括干扰DNA修复系统。然而，慢性后镉暴露的影响仍然未知。在这里，我们建立了一个独特的慢性Cd暴露后的人肺细胞模型（“CR0”细胞），并研究慢性Cd暴露后对DNA修复系统的影响。我们发现，即使在无cd培养基中培养一年多，CR0细胞仍保持抗cd特性。由于DNA修复能力降低和DNA修复基因表达谱异常，CR0细胞存在持续的DNA损伤。共鉴定出12个与慢性Cd暴露后相关的DNA修复基因，它们可能是识别慢性Cd暴露后的潜在生物标志物。临床数据库分析表明，一些DNA修复基因在不同吸烟史的肺癌患者中发挥作用。一般来说，CR0细胞对化疗药物（顺铂、吉西他滨、酒石酸长春瑞滨）和DNA损伤（H2O2）药物更为敏感，这可能是预防和治疗癌症的一把双刃剑。总的来说，我们首次证明慢性后镉暴露对人肺细胞的影响是持久的，不同于急性和慢性暴露。我们的研究结果揭示了Cd诱导致癌的新视角- Cd慢性暴露后。这项研究鼓励了暴露后研究领域，这是至关重要的，但长期被忽视。
Cadmium (Cd) is a widespread environmental pollutant and carcinogen. Although the exact mechanisms of Cd-induced carcinogenesis remain unclear, previous acute/chronic Cd exposure studies have shown that Cd exerts its cytotoxic and carcinogenic effects through multiple mechanisms, including interference with the DNA repair system. However, the effects of post-chronic Cd exposure remain unknown. Here, we establish a unique post-chronic Cd-exposed human lung cell model (the “CR0” cells) and investigate the effects of post-chronic Cd exposure on the DNA repair system. We found that the CR0 cells retained Cd-resistant property even though it was grown in Cd-free culture medium for over a year. The CR0 cells had lasting DNA damage due to reduced DNA repair capacity and an aberrant DNA repair gene expression profile. A total of 12 DNA repair genes associated with post-chronic Cd exposure were identified, and they could be potential biomarkers for identifying post-chronic Cd exposure. Clinical database analysis suggests that some of the DNA repair genes play a role in lung cancer patients with different smoking histories. Generally, CR0 cells were more sensitive to chemotherapeutic (cisplatin, gemcitabine, and vinorelbine tartrate) and DNA damaging (H2O2) agents, which may represent a double-edged sword for cancer prevention and treatment. Overall, we demonstrated for the first time that the effects of post-chronic Cd exposure on human lung cells are long-lasting and different from that of acute and chronic exposures. Findings from our study unveiled a new perspective on Cd-induced carcinogenesis—the post-chronic exposure of Cd. This study encourages the field of post-exposure research which is crucial but has long been ignored.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
5.8
作者：
Lin YS;Caffrey JL;Chang MH;Dowling N;Lin JW
通讯作者：
Lin JW
影响因子：
10.4
作者：
Tellez-Plaza M;Tang WY;Shang Y;Umans JG;Francesconi KA;Goessler W;Ledesma M;Leon M;Laclaustra M;Pollak J;Guallar E;Cole SA;Fallin MD;Navas-Acien A
通讯作者：
Navas-Acien A
DOI：
10.4238/2012.september.25.2
发表时间：
2012-12
期刊：
Genetics and molecular research : GMR
影响因子：
--
作者：
X. Yang;Y. Ge;H. Zhang;H. Ning;J. Jiang;Y. Qi;Z. L. Wang
通讯作者：
X. Yang;Y. Ge;H. Zhang;H. Ning;J. Jiang;Y. Qi;Z. L. Wang
影响因子：
14.8
作者：
Olive, Peggy L.;Banath, Judit P.
通讯作者：
Banath, Judit P.