Department of Food Chemistry and Toxicology, Institute of Applied Biosciences (IAB), Karlsruhe Institute of Technology (KIT), 76131 Karlsruhe, Germany.
Int J Mol Sci. 2024 Sep 20;25(18):10129. doi: 10.3390/ijms251810129.
Chromate has been shown to dysregulate epigenetic mechanisms such as DNA methylation, leading to changes in gene expression and genomic instability. However, most in vitro studies are limited to short incubation periods, although chronic exposure may be more relevant for both environmental and occupational exposure. In this study, human adenocarcinoma A549 cells were treated with 1, 2 or 5 µM chromate for 24 h and compared with incubations with 0.2, 0.5 or 1 µM chromate for 1 to 5 weeks. Chromium accumulated in a pronounced time- and concentration-dependent manner after short-term treatment, whereas a plateau of intracellular chromium content was observed after long-term treatment. While short-term treatment induced a G2 arrest of the cell cycle, this effect was not observed after long-term treatment at lower concentrations. The opposite was observed for global DNA methylation: while short-term treatment showed no effect of chromate, significant dose-dependent hypomethylation was observed in the long-term experiments. Time-dependent effects were also observed in a high-throughput RT-qPCR gene expression analysis, particularly in genes related to the inflammatory response and DNA damage response. Taken together, the results suggest specific differences in toxicity profiles when comparing short-term and long-term exposure to chromate in A549 cells.
铬酸盐已被证明会扰乱表观遗传机制，如 DNA 甲基化，导致基因表达和基因组不稳定性的变化。然而，大多数体外研究的孵育时间都比较短，尽管慢性暴露对于环境和职业暴露可能更为相关。在这项研究中，用人肺腺癌细胞 A549 处理 1、2 或 5µM 的铬酸盐 24 小时，并与 0.2、0.5 或 1µM 的铬酸盐孵育 1 至 5 周进行比较。短期处理后，铬酸盐在明显的时间和浓度依赖性方式下积累，而长期处理后观察到细胞内铬含量的平台。虽然短期处理会导致细胞周期的 G2 期阻滞，但在较低浓度的长期处理中没有观察到这种效果。总的 DNA 甲基化则呈现相反的情况：虽然短期处理对铬酸盐没有影响，但在长期实验中观察到显著的剂量依赖性去甲基化。高通量 RT-qPCR 基因表达分析也观察到时间依赖性效应，特别是在与炎症反应和 DNA 损伤反应相关的基因中。总之，这些结果表明，在 A549 细胞中比较短期和长期暴露于铬酸盐时，毒性特征存在特定差异。
