钨诱导人支气管上皮细胞发生癌变。

Tungsten-induced carcinogenesis in human bronchial epithelial cells.

作者信息

Laulicht Freda, Brocato Jason, Cartularo Laura, Vaughan Joshua, Wu Feng, Kluz Thomas, Sun Hong, Oksuz Betul Akgol, Shen Steven, Peana Massimiliano, Medici Serenella, Zoroddu Maria Antonietta, Costa Max

机构信息

Department of Environmental Medicine, New York University Langone Medical Center, Tuxedo, NY 10987, USA.

Genome Technology Center, New York University Langone Medical Center, New York, NY 10016, USA.

出版信息

Toxicol Appl Pharmacol. 2015 Oct 1;288(1):33-9. doi: 10.1016/j.taap.2015.07.003. Epub 2015 Jul 9.

Abstract

Metals such as arsenic, cadmium, beryllium, and nickel are known human carcinogens; however, other transition metals, such as tungsten (W), remain relatively uninvestigated with regard to their potential carcinogenic activity. Tungsten production for industrial and military applications has almost doubled over the past decade and continues to increase. Here, for the first time, we demonstrate tungsten's ability to induce carcinogenic related endpoints including cell transformation, increased migration, xenograft growth in nude mice, and the activation of multiple cancer-related pathways in transformed clones as determined by RNA sequencing. Human bronchial epithelial cell line (Beas-2B) exposed to tungsten developed carcinogenic properties. In a soft agar assay, tungsten-treated cells formed more colonies than controls and the tungsten-transformed clones formed tumors in nude mice. RNA-sequencing data revealed that the tungsten-transformed clones altered the expression of many cancer-associated genes when compared to control clones. Genes involved in lung cancer, leukemia, and general cancer genes were deregulated by tungsten. Taken together, our data show the carcinogenic potential of tungsten. Further tests are needed, including in vivo and human studies, in order to validate tungsten as a carcinogen to humans.

摘要

诸如砷、镉、铍和镍等金属是已知的人类致癌物;然而,其他过渡金属,如钨(W),在其潜在致癌活性方面仍相对缺乏研究。过去十年间,用于工业和军事用途的钨产量几乎翻了一番,且仍在持续增长。在此,我们首次证明了钨具有诱导致癌相关终点的能力,包括细胞转化、迁移增加、裸鼠体内异种移植瘤生长,以及通过RNA测序确定的转化克隆中多种癌症相关途径的激活。暴露于钨的人支气管上皮细胞系(Beas-2B)产生了致癌特性。在软琼脂试验中,经钨处理的细胞形成的集落比对照更多,且钨转化的克隆在裸鼠体内形成了肿瘤。RNA测序数据显示,与对照克隆相比,钨转化的克隆改变了许多癌症相关基因的表达。与肺癌、白血病相关的基因以及一般癌症基因均因钨而失调。综上所述,我们的数据显示了钨的致癌潜力。为了验证钨对人类的致癌性,还需要进行进一步的测试,包括体内研究和人体研究。

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