Jin Li-Fang, Wang Yuan-Yuan, Zhang Zi-Dong, Yuan Yi-Meng, Hu Yi-Rui, Wei Yang-Feng, Ni Jian
College of Life Science of Shaoxing University, Shaoxing Zhejiang 312000, China.
Dongwuxue Yanjiu. 2013 Jun;34(E3):E93-100.
Chronic ingestion of high concentrations of hexavalent chromium [Cr(VI)] in drinking water induces intestinal tumors in mice; however, information on its toxicity on intestinal smooth muscle cells is limited. The present study aimed to assess the in vitro and in vivo toxicological effects of Cr(VI) on intestinal smooth muscle cells. Human intestinal smooth muscle cells (HISM cells) were cultured with different concentrations of Cr(VI) to evaluate effects on cell proliferation ability, oxidative stress levels, and antioxidant system. Furthermore, tissue sections in Cr(VI) exposed rabbits were analyzed to evaluate toxicity on intestinal muscle cells in vivo. Gene chips were utilized to assess differential gene expression profiles at the genome-wide level in 1 μmol/L Cr(VI) treated cells. Intestinal tissue biopsy results showed that Cr(VI) increased the incidences of diffuse epithelial hyperplasia in intestinal jejunum but caused no obvious damage to the structure of the muscularis. Cell proliferation analysis revealed that high concentrations (≥64 μmol/L) but not low concentrations of Cr(VI) (≤16 μmol/L) significantly inhibited the growth of HISM cells. For oxidative stress levels, the expression of reactive oxygen species (ROS) and nitric oxide (NO) was elevated at high concentrations (≥64 μmol/L) but not at low concentrations of Cr(VI) (≤16 μmol/L). In addition, dose-dependent increases in the activity of oxidized glutathione (GSSH)/total-glutathione (T-GSH) were also observed. Gene chip screened 491 differentially expressed genes including genes associated with cell apoptosis, oxidations, and cytoskeletons. Some of these differentially expressed genes may be unique to smooth muscle cells in response to Cr(VI) induction.
长期摄入饮用水中高浓度的六价铬[Cr(VI)]会诱发小鼠肠道肿瘤；然而，关于其对肠道平滑肌细胞毒性的信息有限。本研究旨在评估Cr(VI)对肠道平滑肌细胞的体外和体内毒理学效应。用不同浓度的Cr(VI)培养人肠道平滑肌细胞（HISM细胞），以评估其对细胞增殖能力、氧化应激水平和抗氧化系统的影响。此外，对暴露于Cr(VI)的兔子的组织切片进行分析，以评估其对体内肠道肌肉细胞的毒性。利用基因芯片评估在1 μmol/L Cr(VI)处理的细胞中全基因组水平上的差异基因表达谱。肠道组织活检结果显示，Cr(VI)增加了空肠弥漫性上皮增生的发生率，但对肌层结构没有明显损害。细胞增殖分析表明，高浓度（≥64 μmol/L）而非低浓度（≤16 μmol/L）的Cr(VI)显著抑制HISM细胞的生长。对于氧化应激水平，高浓度（≥64 μmol/L）而非低浓度（≤16 μmol/L）的Cr(VI)会使活性氧（ROS）和一氧化氮（NO）的表达升高。此外，还观察到氧化型谷胱甘肽（GSSH）/总谷胱甘肽（T-GSH）活性呈剂量依赖性增加。基因芯片筛选出491个差异表达基因，包括与细胞凋亡、氧化和细胞骨架相关的基因。其中一些差异表达基因可能是平滑肌细胞对Cr(VI)诱导的独特反应。
