Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA.
BMC Genomics. 2011 Apr 1;12:173. doi: 10.1186/1471-2164-12-173.
Exposure to the toxic metals arsenic and cadmium is associated with detrimental health effects including cancers of various organs. While arsenic and cadmium are well known to cause adverse health effects at high doses, the molecular impact resulting from exposure to environmentally relevant doses of these metals remains largely unexplored.
In this study, we examined the effects of in vitro exposure to either arsenic or cadmium in human TK6 lymphoblastoid cells using genomics and systems level pathway mapping approaches. A total of 167 genes with differential expression were identified following exposure to either metal with surprisingly no overlap between the two. Real-time PCR was used to confirm target gene expression changes. The gene sets were overlaid onto protein-protein interaction maps to identify metal-induced transcriptional networks. Interestingly, both metal-induced networks were significantly enriched for proteins involved in common biological processes such as tumorigenesis, inflammation, and cell signaling. These findings were further supported by gene set enrichment analysis.
This study is the first to compare the transcriptional responses induced by low dose exposure to cadmium and arsenic in human lymphoblastoid cells. These results highlight that even at low levels of exposure both metals can dramatically influence the expression of important cellular pathways.
接触有毒金属砷和镉与各种器官的癌症等有害健康影响有关。虽然砷和镉在高剂量下众所周知会对健康产生不良影响，但暴露于环境相关剂量的这些金属所产生的分子影响在很大程度上仍未得到探索。
在这项研究中，我们使用基因组学和系统水平途径映射方法研究了体外暴露于砷或镉对人 TK6 淋巴母细胞的影响。在暴露于任何一种金属后，有 167 个基因的表达存在差异，令人惊讶的是，这两种金属之间没有重叠。实时 PCR 用于确认靶基因表达变化。将基因集叠加到蛋白质-蛋白质相互作用图上，以确定金属诱导的转录网络。有趣的是，两种金属诱导的网络都显著富集了参与常见生物学过程（如肿瘤发生、炎症和细胞信号传导）的蛋白质。基因集富集分析进一步支持了这些发现。
这项研究是首次比较低剂量暴露于镉和砷在人淋巴母细胞中诱导的转录反应。这些结果强调，即使在低暴露水平下，这两种金属都可以极大地影响重要细胞途径的表达。
