Detection of γ-H2AX, a Biomarker for DNA Double-strand Breaks, in Urinary Bladders of N -Butyl- N -(4-Hydroxybutyl)-Nitrosamine-Treated Rats.

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.

• Authors: Takeshi Toyoda, Jun-Ichi Akagi, Young-Man Cho, Yasuko Mizuta, Saeko Onami, Isamu Suzuki, Kumiko Ogawa
• Journal: Journal of toxicologic pathology (J Toxicol Pathol) Vol. 26 Issue 2 Pg. 215-21 (Jun 2013) ISSN: 0914-9198 [Print] Japan
• PMID: 23914065 (Publication Type: Journal Article)