Department of Physical Therapy, College of Health Sciences, University of Kentucky, Lexington, Kentucky.
Center for Muscle Biology, University of Kentucky, Lexington, Kentucky.
Physiol Genomics. 2020 Dec 1;52(12):575-587. doi: 10.1152/physiolgenomics.00096.2020. Epub 2020 Oct 5.
As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military-grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 mo. We found that most transcriptional changes occur at 1 and 3 mo after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 mo. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. These data suggest that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.
由于军事行动，许多退伍军人患有穿透性伤口，并长期保留军用重金属碎片。碎片的大小和位置各不相同，在所有情况下，完全手术切除可能不可行或无益。越来越多的证据表明，重金属碎片的保留可能具有严重的生物学意义，包括恶性转化风险增加。以前的研究评估了金属合金在大鼠中的致瘤作用，表明多种金属的组合足以在骨骼肌肉组织中长时间保留后诱导肿瘤形成。在这项研究中，我们分析了骨骼肌肉组织对 8 种不同与军事相关的纯金属的转录变化，研究发现，大多数转录变化发生在金属颗粒嵌入骨骼肌肉后 1 个月和 3 个月，这些影响在 6 个月和 12 个月时得到解决。我们还报告了镍和钴的显著免疫原性效应，以及铅和贫铀对基因表达的抑制作用。总的来说，骨骼肌肉表现出对内部金属碎片的适应和恢复的惊人能力；然而，细胞对慢性暴露的反应可能仅限于金属-组织界面。这些数据表明，除非受影响的区域被活检特异性捕获，否则很难可靠地检测到肌肉基因表达的变化，这些变化表明长期不良健康结果。
