Toyoda Takeshi, Akagi Jun-Ichi, Cho Young-Man, Mizuta Yasuko, Onami Saeko, Suzuki Isamu, Ogawa Kumiko
Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan.
J Toxicol Pathol. 2013 Jun;26(2):215-21. doi: 10.1293/tox.26.215. Epub 2013 Jul 10.
To evaluate the potential role of DNA repair in bladder carcinogenesis, we performed an immunohistochemical analysis of expression of various DNA repair enzymes and γ-H2AX, a high-sensitivity marker of DNA double-strand breaks, in the urothelium of male F344 rats treated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), a bladder-specific carcinogen. Our results clearly demonstrated that γ-H2AX aggregation was specifically generated in nuclei of bladder epithelial cells of BBN-treated rats, which was not found in untreated controls or mesenchymal cells. γ-H2AX-positive cells were detected not only in hyperplastic and neoplastic areas but also in the normal-like urothelium after BBN treatment. These data indicate that γ-H2AX has potential as a useful biomarker for early detection of genotoxicity in the rat urinary bladder. To the best of our knowledge, this is the first report demonstrating expression of γ-H2AX during bladder carcinogenesis.
为了评估DNA修复在膀胱癌发生中的潜在作用，我们对用膀胱特异性致癌物N-丁基-N-(4-羟丁基)亚硝胺（BBN）处理的雄性F344大鼠的尿路上皮中各种DNA修复酶和γ-H2AX（一种DNA双链断裂的高灵敏度标志物）的表达进行了免疫组织化学分析。我们的结果清楚地表明，γ-H2AX聚集特异性地出现在BBN处理大鼠的膀胱上皮细胞核中，在未处理的对照或间充质细胞中未发现。γ-H2AX阳性细胞不仅在增生和肿瘤区域被检测到，在BBN处理后的正常样尿路上皮中也被检测到。这些数据表明，γ-H2AX有潜力作为大鼠膀胱遗传毒性早期检测的有用生物标志物。据我们所知，这是第一份证明γ-H2AX在膀胱癌发生过程中表达的报告。
