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尿总砷和 8-羟基脱氧鸟苷与无明显砷暴露地区的肾细胞癌有关。

Urinary total arsenic and 8-hydroxydeoxyguanosine are associated with renal cell carcinoma in an area without obvious arsenic exposure.

机构信息

Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.

出版信息

Toxicol Appl Pharmacol. 2012 Aug 1;262(3):349-54. doi: 10.1016/j.taap.2012.05.013. Epub 2012 May 30.

Abstract

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.

摘要

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。

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