Gamma-H2AX Expression as a Biomarker of Carcinogenesis: Applications to Toxicology

Suzuki, Shugo; Wanibuchi, Hideki

doi:10.1007/978-3-030-87225-0_8-1

Shugo Suzuki⁶ &
Hideki Wanibuchi⁶

Part of the book series: Biomarkers in Disease: Methods, Discoveries and Applications ((BDMDA))

61 Accesses

Abstract

Cancer develops due to the accumulation of genetic and epigenetic changes caused by various factors. An important source of genetic changes is DNA double-strand breaks (DBSs). Radiation, oxidative stress, and carcinogens in the environment cause DNA DSBs. Cells respond to DSBs by phosphorylating histone H2AX to produce γH2AX. In in vitro assays, analysis of γH2AX formation enables detection of genotoxic carcinogens with a high accuracy. In in vivo assays, both genotoxic and non-genotoxic carcinogens can be detected. γH2AX is highly expressed in a variety of human precancerous and cancerous lesions. Here we explore the use of γH2AX formation as a biomarker of human tumorigenesis and as a prognostic marker for several cancers.

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Abbreviations

53BP1:: p53-binding protein 1
ATM:: Ataxia-telangiectasia-mutated
ATR:: ATM and Rad3-related
ATRIP:: ATR-interacting protein
BRCA1:: Breast cancer associated 1
DNA-PK:: DNA-dependent protein kinase
DSBs:: DNA double-strand breaks
ECVAM:: European Centre for the Validation of Alternative Methods
ELISA:: Enzyme-linked immunosorbent assay
HR:: Homologous recombination
IARC:: International Agency for Research on Cancer
LC-MS/MS:: Liquid chromatography-tandem mass spectrometric
MDC1:: Mediator of DNA damage checkpoint protein 1
MRE11:: Meiotic recombination 11
MRN:: MRE11-RAD50-NBS1
NBS1:: Nijmegen breakage syndrome 1
NHEJ:: Non-homologous end joining
RNF168:: Ring finger protein 168
RNF8:: Ring finger protein 8
ROS:: Reactive oxygen species
RPA:: Replication protein A
UV:: Ultraviolet

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Acknowledgments

This work was supported by the Health Labour Sciences Research Grants from the Ministry of Health, Labor and Welfare, Japan (Program Grant Number: JPMH17933911 and JPMH20317159).

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Authors and Affiliations

Department of Molecular Pathology, Osaka City University Graduate School of Medicine, Osaka, Japan
Shugo Suzuki & Hideki Wanibuchi

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Shugo Suzuki
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Hideki Wanibuchi
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Correspondence to Hideki Wanibuchi .

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Editors and Affiliations

Department of Biomedical Sciences, University of Westminster, London, UK
Vinood B. Patel
Sch Biomed & Health Sci, Wilkins Bldg, King's College London Franklin, London, UK
Victor R. Preedy
Department of Medicine, King Abdulaziz Med City, Riyadh, Saudi Arabia
Rajkumar Rajendram

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Suzuki, S., Wanibuchi, H. (2022). Gamma-H2AX Expression as a Biomarker of Carcinogenesis: Applications to Toxicology. In: Patel, V.B., Preedy, V.R., Rajendram, R. (eds) Biomarkers in Toxicology. Biomarkers in Disease: Methods, Discoveries and Applications. Springer, Cham. https://doi.org/10.1007/978-3-030-87225-0_8-1

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DOI: https://doi.org/10.1007/978-3-030-87225-0_8-1
Received: 15 October 2021
Accepted: 29 October 2021
Published: 05 March 2022
Publisher Name: Springer, Cham
Print ISBN: 978-3-030-87225-0
Online ISBN: 978-3-030-87225-0
eBook Packages: Springer Reference Biomedicine and Life SciencesReference Module Biomedical and Life Sciences

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