Environmentally Relevant Levels of Depleted Uranium Impacts Dermal Fibroblast Proliferation, Viability, Metabolic Activity, and Scratch Closure.

Environmentally Relevant Levels of Depleted Uranium Impacts Dermal Fibroblast Proliferation, Viability, Metabolic Activity, and Scratch Closure.
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贫铀的环境相关水平影响皮肤成纤维细胞增殖、活力、代谢活性和划痕闭合。

DOI:
10.3390/toxics9090211
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发表时间:
2021-09-03
期刊:
影响因子:
4.6
通讯作者:
Kellar R
Kellar R
中科院分区:
环境科学与生态学3区
文献类型:
--
作者:
Cruz N;Buscaglia R;Salanga M;Kellar R

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铀 (U) 是一种用于军事和工业环境的重金属,其中很大一部分是从美国西南部地区开采的。铀可用于能源和军事武器,但采矿过程已将铀释放到土壤和地表水中,可能对人类和环境健康构成威胁。大多数关于美国人类健康问题的文献都关注基于无意摄入或吸入的结果,并且关于其通过皮肤接触产生的影响的数据有限。我们利用皮肤真皮细胞评估了 U 的局部化学毒性。采用硝酸铀酰 (UN) 形式的可溶性贫铀 (DU),我们假设体外暴露的 UN 将通过影响细胞活力和代谢活动对原代真皮成纤维细胞产生细胞毒性作用,并且进一步可能通过改变细胞增殖和迁移来延迟伤口愈合。利用水中发现的环境相关水平的 U(0.1 M 至 100 M [UN];23.8–23,800 ppb [U]),我们通过生长曲线和体外划痕测定来量化细胞有丝分裂和迁移。细胞暴露 24 小时至 144 小时,对联合国化学毒性进行时程评估。在高于和低于环境保护局安全暴露限值阈值的浓度下观察到了联合国的影响。联合国暴露导致活细胞计数呈剂量依赖性下降;然而,当针对存在的活细胞进行校正时,它会产生新陈代谢的增加。此外,细胞增殖、群体倍增和闭合百分比在≥10 M UN 水平时受到阻碍。因此,无意的接触可能会加剧高危人群中已有的皮肤病,此外,它可能会严重干扰皮肤组织的修复过程。
Uranium (U) is a heavy metal used in military and industrial settings, with a large portion being mined from the Southwest region of the United States. Uranium has uses in energy and military weaponry, but the mining process has released U into soil and surface waters that may pose threats to human and environmental health. The majority of literature regarding U’s human health concern focuses on outcomes based on unintentional ingestion or inhalation, and limited data are available about its influence via cutaneous contact. Utilizing skin dermis cells, we evaluated U’s topical chemotoxicity. Employing soluble depleted uranium (DU) in the form of uranyl nitrate (UN), we hypothesized that in vitro exposure of UN will have cytotoxic effects on primary dermal fibroblasts by affecting cell viability and metabolic activity and, further, may delay wound healing aspects via altering cell proliferation and migration. Using environmentally relevant levels of U found in water (0.1 M to 100 M [UN]; 23.8–23,800 ppb [U]), we quantified cellular mitosis and migration through growth curves and in vitro scratch assays. Cells were exposed from 24 h to 144 h for a time-course evaluation of UN chemical toxicity. The effects of UN were observed at concentrations above and below the Environmental Protection Agency threshold for safe exposure limits. UN exposure resulted in a dose-dependent decrease in the viable cell count; however, it produced an increase in metabolism when corrected for the viable cells present. Furthermore, cellular proliferation, population doubling, and percent closure was hindered at levels ≥10 M UN. Therefore, inadvertent exposure may exacerbate pre-existing skin diseases in at-risk demographics, and additionally, it may substantially interfere in cutaneous tissue repair processes.
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