Research Article
Detection of γ-H2AX, a Biomarker for DNA Double-strand Breaks, in Urinary Bladders of -Butyl--(4-Hydroxybutyl)-Nitrosamine-Treated Rats
Takeshi Toyoda, Jun-ichi Akagi, Young-Man Cho, Yasuko Mizuta, Saeko Onami, Isamu Suzuki, Kumiko Ogawa
Published:
July 10, 2013
DOI:
10.1293/tox.26.215
License:
©2013 The Japanese Society of Toxicologic Pathology2013This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives (by-nc-nd) License.
Abstract
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.