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Role of γ-H2AX as a biomarker for detection of bladder carcinogens in F344 rats

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 pres...

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Detalles Bibliográficos
Autores principales: Suzuki, Shugo, Gi, Min, Toyoda, Takeshi, Kato, Hiroyuki, Naiki-Ito, Aya, Kakehashi, Anna, Ogawa, Kumiko, Takahashi, Satoru, Wanibuchi, Hideki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japanese Society of Toxicologic Pathology 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7677623/
https://www.ncbi.nlm.nih.gov/pubmed/33239845
http://dx.doi.org/10.1293/tox.2020-0038
Descripción
Sumario: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.