Department of Health Toxicology, School of Public Health, Central South University, Changsha, Hunan 410078, PR China.
Mol Med Rep. 2013 Jul;8(1):53-60. doi: 10.3892/mmr.2013.1462. Epub 2013 May 8.
Hexavalent chromium [Cr(VI)] and its compounds have extensive applications in many industries and are widely known to cause occupational diseases as well as carcinogenic effects in humans. Mitochondrial damage, which is important in Cr(VI)‑induced cytotoxicity, may be characterized by the opening status of the permeability transition pore, the maintenance of the mitochondrial membrane potential and the level of malondialdehyde. The formation of DNA‑protein crosslinks (DPCs) in target tissues appears to be the direct and primary genotoxic effect of Cr(VI) exposure, and the lymphocytic DPCs may be viewed as a biomarker of internal Cr(VI) accumulation. It is well known that vitamin C (vit C) is an important biological reducing agent in humans and animals, which is capable of reducing Cr(VI). Regardless of the evidence from cell culture and in vivo experiments of the protective effect of the antioxidant, vit C, following exposure to Cr(VI), no studies have been conducted to date to demonstrate the time‑order effects of vit C on Cr(VI)‑induced mitochondrial damage and DPC formation. In the present study, by using peripheral blood lymphocytes from Sprague‑Dawley rats, we demonstrated that vit C pre‑ and co‑treatment have a protective effect against Cr(VI)‑induced loss of cell viability and mitochondrial damage, while only vit C co‑treatment has a protective effect against the Cr(VI)‑induced increase in DPCs. The mechanistic investigation revealed that cellular reactive oxygen species levels are correlated with Cr(VI)‑induced mitochondrial damage, and that p53 expression is correlated with the Cr(VI)‑induced increase in DPCs. We concluded that vit C exerts different time‑order effects on Cr(VI)‑induced mitochondrial damage and DPC formation, and that biomarkers, including DPC and p53, may be used in the assessment of the development of Cr(VI)‑induced cancer. These findings facilitate more detailed follow‑up of the Cr(VI)‑exposure populations for secondary prevention.
六价铬（Cr(VI)）及其化合物在许多行业中有广泛的应用，已知会导致职业性疾病和人类致癌作用。线粒体损伤在 Cr(VI)诱导的细胞毒性中很重要，可能表现为通透性转换孔的开放状态、线粒体膜电位的维持和丙二醛的水平。靶组织中 DNA-蛋白质交联物（DPC）的形成似乎是 Cr(VI)暴露的直接和主要遗传毒性作用，淋巴细胞 DPC 可被视为 Cr(VI)内蓄积的生物标志物。众所周知，维生素 C（vit C）是人和动物体内重要的生物还原剂，能够还原 Cr(VI)。尽管有细胞培养和体内实验的证据表明抗氧化剂 vit C 对 Cr(VI)暴露具有保护作用，但迄今为止，尚无研究表明 vit C 对 Cr(VI)诱导的线粒体损伤和 DPC 形成的时间顺序效应。在本研究中，我们使用 Sprague-Dawley 大鼠的外周血淋巴细胞，证明了 vit C 预处理和共处理对 Cr(VI)诱导的细胞活力丧失和线粒体损伤具有保护作用，而仅 vit C 共处理对 Cr(VI)诱导的 DPC 增加具有保护作用。机制研究表明，细胞内活性氧水平与 Cr(VI)诱导的线粒体损伤相关，p53 表达与 Cr(VI)诱导的 DPC 增加相关。我们得出结论，vit C 对 Cr(VI)诱导的线粒体损伤和 DPC 形成有不同的时间顺序效应，DPC 和 p53 等生物标志物可用于评估 Cr(VI)诱导的癌症的发展。这些发现有助于对 Cr(VI)暴露人群进行更详细的二级预防随访。
