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 months. We found that most transcriptional changes occur at 1 and 3 months after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 months. 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. This data suggests 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.

中文翻译：

---

嵌入金属对骨骼肌基因表达影响的时程分析

由于军事行动，许多退伍军人遭受穿透性伤口和长期保留军用级重金属碎片的痛苦。碎片的大小和位置各不相同，完全手术切除可能并非在所有情况下都可行或有益。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，包括增加恶性转化的风险。先前的研究评估了金属合金在大鼠中的致瘤作用，证明金属的组合足以在骨骼肌组织中长期保留后诱导肿瘤形成。在这项研究中，我们分析了骨骼肌组织在 12 个月内响应八种不同的军事相关纯金属的转录变化。我们发现大多数转录变化发生在金属颗粒嵌入骨骼肌后 1 和 3 个月，这些影响在 6 和 12 个月时消退。我们还报告了镍和钴的显着免疫原性作用以及铅和贫铀对基因表达的抑制作用。总体而言，骨骼肌表现出非凡的适应内在金属碎片并从中恢复的能力。然而，细胞对慢性暴露的反应可能仅限于金属-组织界面。该数据表明，除非通过活组织检查专门捕获受影响的区域，否则很难可靠地检测肌肉基因表达的变化，而这些变化将表明长期不利的健康结果。我们还报告了镍和钴的显着免疫原性作用以及铅和贫铀对基因表达的抑制作用。总体而言，骨骼肌表现出非凡的适应内在金属碎片并从中恢复的能力。然而，细胞对慢性暴露的反应可能仅限于金属-组织界面。该数据表明，除非通过活组织检查专门捕获受影响的区域，否则很难可靠地检测肌肉基因表达的变化，而这些变化将表明长期不利的健康结果。我们还报告了镍和钴的显着免疫原性作用以及铅和贫铀对基因表达的抑制作用。总体而言，骨骼肌表现出非凡的适应内在金属碎片并从中恢复的能力。然而，细胞对慢性暴露的反应可能仅限于金属-组织界面。该数据表明，除非通过活组织检查专门捕获受影响的区域，否则很难可靠地检测肌肉基因表达的变化，而这些变化将表明长期不利的健康结果。细胞对慢性暴露的反应可能仅限于金属-组织界面。该数据表明，除非通过活组织检查专门捕获受影响的区域，否则很难可靠地检测肌肉基因表达的变化，而这些变化将表明长期不利的健康结果。细胞对慢性暴露的反应可能仅限于金属-组织界面。该数据表明，除非通过活组织检查专门捕获受影响的区域，否则很难可靠地检测肌肉基因表达的变化，而这些变化将表明长期不利的健康结果。