Okamoto K, Toyokuni S, Uchida K, Ogawa O, Takenewa J, Kakehi Y, Kinoshita H, Hattori-Nakakuki Y, Hiai H, Yoshida O
Department of Urology, Faculty of Medicine, Kyoto University, Japan.
Int J Cancer. 1994 Sep 15;58(6):825-9. doi: 10.1002/ijc.2910580613.
To study the possible involvement of reactive oxygen species (ROS) in the tumor biology of human renal-cell carcinoma (RCC), we analyzed 35 cases of RCC for 2 parameters of oxidative damage: 8-hydroxy-2'-deoxyguanosine (8-OHdG), a mutation-prone DNA-base-modified product, was measured by means of high-performance liquid chromatography (HPLC) with an electrochemical (EC) detector, and 4-hydroxy-2-nonenal (HNE)-modified proteins were measured with a polyclonal antibody against HNE-modified proteins. A 54% higher content of 8-OHdG was found in RCC than in the corresponding non-tumorous kidney, suggesting that the DNA of RCC is more exposed to ROS than is the DNA of non-tumorous kidneys. Immunohistochemistry for HNE-modified proteins showed a distinct staining pattern of fine to coarse granularity in the cytoplasm of RCC (n = 15), implying that lipid peroxidation products are located in cytoplasmic organelles. These results suggest that RCC constitutionally elaborates more ROS than is produced by the non-tumorous parts of kidneys. No correlation was found between clinical stage, histology, age or sex and the 2 parameters examined.
为研究活性氧（ROS）在人类肾细胞癌（RCC）肿瘤生物学中的可能作用，我们分析了35例RCC的2个氧化损伤参数：采用高效液相色谱（HPLC）和电化学（EC）检测器测定了易发生突变的DNA碱基修饰产物8-羟基-2'-脱氧鸟苷（8-OHdG），并用抗HNE修饰蛋白的多克隆抗体测定了4-羟基-2-壬烯醛（HNE）修饰蛋白。结果发现，RCC中8-OHdG的含量比相应的非肿瘤性肾组织高54%，这表明RCC的DNA比非肿瘤性肾组织的DNA更容易受到ROS的影响。对HNE修饰蛋白进行免疫组织化学分析显示，RCC（n = 15）细胞质中呈现出从细颗粒到粗颗粒的明显染色模式，这意味着脂质过氧化产物位于细胞质细胞器中。这些结果表明，RCC本质上比肾组织的非肿瘤部分产生更多的ROS。在临床分期、组织学、年龄或性别与所检测的2个参数之间未发现相关性。
