Detection of γ-H2AX, a biomarker for DNA double-strand breaks, in urinary bladders of N-butyl-N-(4-hydroxybutyl)-nitrosamine-treated rats

T Toyoda, J Akagi, YM Cho, Y Mizuta… - Journal of toxicologic …, 2013 - jstage.jst.go.jp
T Toyoda, J Akagi, YM Cho, Y Mizuta, S Onami, I Suzuki, K Ogawa
Journal of toxicologic pathology, 2013jstage.jst.go.jp
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 …
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.(DOI: 10.1293/tox. 26.215; J Toxicol Pathol 2013; 26: 215–221)
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