Bardack Stephanie, Dalgard Clifton L, Kalinich John F, Kasper Christine E
Office of the Assistant Secretary for Preparedness and Response, Department of Health and Human Services, Washington, D.C. 20201, USA.
Department of Anatomy, Physiology, and Genetics, School of Medicine, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Road, Bethesda, MD 20814, USA.
Int J Environ Res Public Health. 2014 Mar 10;11(3):2922-40. doi: 10.3390/ijerph110302922.
Tungsten-based materials have been proposed as replacements for depleted uranium in armor-penetrating munitions and for lead in small-arms ammunition. A recent report demonstrated that a military-grade composition of tungsten, nickel, and cobalt induced a highly-aggressive, metastatic rhabdomyosarcoma when implanted into the leg muscle of laboratory rats to simulate a shrapnel wound. The early genetic changes occurring in response to embedded metal fragments are not known. In this study, we utilized two cultured rodent myoblast cell lines, exposed to soluble tungsten alloys and the individual metals comprising the alloys, to study the genotoxic effects. By profiling cell transcriptomes using microarray, we found slight, yet distinct and unique, gene expression changes in rat myoblast cells after 24 h metal exposure, and several genes were identified that correlate with impending adverse consequences of ongoing exposure to weapons-grade tungsten alloy. These changes were not as apparent in the mouse myoblast cell line. This indicates a potential species difference in the cellular response to tungsten alloy, a hypothesis supported by current findings with in vivo model systems. Studies examining genotoxic-associated gene expression changes in cells from longer exposure times are warranted.
钨基材料已被提议用作穿甲弹药中贫铀的替代品以及小口径弹药中铅的替代品。最近一份报告表明，一种军事级别的钨、镍和钴成分，在植入实验大鼠腿部肌肉以模拟弹片伤时，会诱发一种高度侵袭性的转移性横纹肌肉瘤。尚不清楚因嵌入金属碎片而发生的早期基因变化情况。在本研究中，我们利用两种培养的啮齿动物成肌细胞系，使其暴露于可溶性钨合金以及构成该合金的单一金属中，以研究遗传毒性效应。通过使用微阵列分析细胞转录组，我们发现金属暴露24小时后大鼠成肌细胞中存在轻微但明显且独特的基因表达变化，并鉴定出了几个与持续接触武器级钨合金即将产生的不良后果相关的基因。这些变化在小鼠成肌细胞系中并不那么明显。这表明在细胞对钨合金的反应中可能存在物种差异，这一假设得到了当前体内模型系统研究结果的支持。有必要开展研究，考察更长暴露时间下细胞中与遗传毒性相关的基因表达变化。
