Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
Toxicol Appl Pharmacol. 2012 Aug 1;262(3):349-54. doi: 10.1016/j.taap.2012.05.013. Epub 2012 May 30.
8-Hydroxydeoxyguanosine (8-OHdG) is one of the most reliable and abundant markers of DNA damage. The study was designed to explore the relationship between urinary 8-OHdG and renal cell carcinoma (RCC) and to investigate whether individuals with a high level of 8-OHdG would have a modified odds ratio (OR) of arsenic-related RCC. This case-control study was conducted with 132 RCC patients and 245 age- and sex-matched controls from a hospital-based pool between November 2006 and May 2009. Pathological verification of RCC was completed by image-guided biopsy or surgical resection of renal tumors. Urinary 8-OHdG levels were determined using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Concentrations of urinary arsenic species, including inorganic arsenic, monomethylarsonic acid (MMA) and dimethylarsinic acid (DMA), were determined by a high performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. Level of urinary 8-OHdG was significantly associated with the OR of RCC in a dose-response relationship after multivariate adjustment. Urinary 8-OHdG was significantly related to urinary total arsenic. The greatest OR (3.50) was seen in the individuals with high urinary 8-OHdG and high urinary total arsenic. A trend test indicated that the OR of RCC was increased with one of these factors and was further increased with both (p=0.002). In conclusion, higher urinary 8-OHdG was a strong predictor of the RCC. High levels of 8-OHdG combined with urinary total arsenic might be indicative of arsenic-induced RCC.
8-羟基脱氧鸟苷(8-OHdG)是 DNA 损伤最可靠和最丰富的标志物之一。本研究旨在探讨尿 8-OHdG 与肾细胞癌(RCC)之间的关系,并研究高 8-OHdG 水平的个体是否具有修饰的砷相关 RCC 的比值比(OR)。这项病例对照研究于 2006 年 11 月至 2009 年 5 月期间在一家医院进行,共有 132 名 RCC 患者和 245 名年龄和性别匹配的对照。通过图像引导活检或肾肿瘤手术切除完成 RCC 的病理验证。采用液相色谱-串联质谱(LC-MS/MS)法测定尿 8-OHdG 水平。采用高效液相色谱-氢化物发生器和原子吸收光谱法测定尿砷形态,包括无机砷、一甲基砷酸(MMA)和二甲基砷酸(DMA)。在多变量调整后,尿 8-OHdG 水平与 RCC 的 OR 呈剂量反应关系,具有显著相关性。尿 8-OHdG 与尿总砷显著相关。在高尿 8-OHdG 和高尿总砷的个体中,观察到最大的 OR(3.50)。趋势检验表明,这些因素中的一个与 RCC 的 OR 增加,并且两个因素都增加(p=0.002)。总之,较高的尿 8-OHdG 是 RCC 的一个强有力的预测因子。高水平的 8-OHdG 结合尿总砷可能提示砷诱导的 RCC。