Excet, Inc., Fort Detrick, Maryland, United States of America.
PLoS One. 2011;6(11):e27730. doi: 10.1371/journal.pone.0027730. Epub 2011 Nov 16.
Many heavy metals, including nickel (Ni), cadmium (Cd), and chromium (Cr) are toxic industrial chemicals with an exposure risk in both occupational and environmental settings that may cause harmful outcomes. While these substances are known to produce adverse health effects leading to disease or health problems, the detailed mechanisms remain unclear. To elucidate the processes involved in the toxicity of nickel, cadmium, and chromium at the molecular level and to perform a comparative analysis, H4-II-E-C3 rat liver-derived cell lines were treated with soluble salts of each metal using concentrations derived from viability assays, and gene expression patterns were determined with DNA microarrays. We identified both common and unique biological responses to exposure to the three metals. Nickel, cadmium, chromium all induced oxidative stress with both similar and unique genes and pathways responding to this stress. Although all three metals are known to be genotoxic, evidence for DNA damage in our study only exists in response to chromium. Nickel induced a hypoxic response as well as inducing genes involved in chromatin structure, perhaps by replacing iron in key proteins. Cadmium distinctly perturbed genes related to endoplasmic reticulum stress and invoked the unfolded protein response leading to apoptosis. With these studies, we have completed the first gene expression comparative analysis of nickel, cadmium, and chromium in H4-II-E-C3 cells.
许多重金属，包括镍（Ni）、镉（Cd）和铬（Cr），都是有毒的工业化学品，在职业和环境环境中都存在暴露风险，可能会导致有害后果。虽然这些物质已知会产生导致疾病或健康问题的不良健康影响，但详细的机制仍不清楚。为了阐明镍、镉、铬在分子水平上的毒性作用的过程，并进行比较分析，使用从生存能力测定中得出的浓度，用可溶性盐处理 H4-II-E-C3 大鼠肝衍生细胞系，并用 DNA 微阵列测定基因表达模式。我们确定了对三种金属暴露的共同和独特的生物学反应。镍、镉、铬均诱导氧化应激，而相似和独特的基因和途径对这种应激作出反应。尽管所有三种金属都被认为具有遗传毒性，但我们的研究中仅存在针对铬的 DNA 损伤证据。镍诱导缺氧反应，并诱导参与染色质结构的基因，这可能是通过在关键蛋白中取代铁。镉明显扰乱与内质网应激相关的基因，并引发未折叠蛋白反应导致细胞凋亡。通过这些研究，我们完成了 H4-II-E-C3 细胞中镍、镉、铬的首次基因表达比较分析。
