Suzuki Shugo, Gi Min, Toyoda Takeshi, Kato Hiroyuki, Naiki-Ito Aya, Kakehashi Anna, Ogawa Kumiko, Takahashi Satoru, Wanibuchi Hideki
Department of Molecular Pathology, Osaka City University Graduate School of Medicine, 1-4-3 Asahi-machi, Abeno-ku, Osaka 545-8585, Japan.
Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-Cho, Mizuho-Ku, Nagoya, Aichi 467-8601, Japan.
J Toxicol Pathol. 2020 Oct;33(4):279-285. doi: 10.1293/tox.2020-0038. Epub 2020 Aug 21.
Phosphorylation of histone H2AX at serine 139 (γ-H2AX) is known to be induced by direct DNA damage or cellular metabolic imbalances and malfunctions. Previous studies have reported that γ-H2AX is a useful biomarker for early detection of genotoxic bladder carcinogens in rats. The purpose of the present study was to determine the role of γ-H2AX as a biomarker for detection of non-genotoxic bladder carcinogens in rats. Six-week-old male F344 rats were treated with 15 different chemicals for 4 weeks. Immunohistochemical analyses revealed that all three genotoxic bladder carcinogens and six out of seven non-genotoxic bladder carcinogens significantly increased γ-H2AX formation in the bladder urothelium of rats. In addition, four out of five rat bladder noncarcinogens did not increase γ-H2AX formation in the bladder urothelium regardless of genotoxicity. These results suggest that γ-H2AX is a useful biomarker for detection of both genotoxic and non-genotoxic bladder carcinogens in rats.
已知组蛋白H2AX在丝氨酸139处的磷酸化（γ-H2AX）可由直接的DNA损伤或细胞代谢失衡及功能异常诱导产生。先前的研究报道，γ-H2AX是大鼠中基因毒性膀胱致癌物早期检测的有用生物标志物。本研究的目的是确定γ-H2AX作为大鼠非基因毒性膀胱致癌物检测生物标志物的作用。六周龄雄性F344大鼠用15种不同化学物质处理4周。免疫组织化学分析显示，所有三种基因毒性膀胱致癌物以及七种非基因毒性膀胱致癌物中的六种均显著增加了大鼠膀胱尿路上皮中γ-H2AX的形成。此外，五种大鼠膀胱非致癌物中的四种无论基因毒性如何，均未增加膀胱尿路上皮中γ-H2AX的形成。这些结果表明，γ-H2AX是大鼠中基因毒性和非基因毒性膀胱致癌物检测的有用生物标志物。
