γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies
Abstract
DNA double strand breaks (DSB) are the gravest form of DNA damage in eukaryotic cells. Failure to detect DSB and activate appropriate DNA damage responses can cause genomic instability, leading to tumorigenesis and possibly accelerated aging. Phosphorylated histone H2AX (γH2AX) is used as a biomarker of cellular response to DSB and its potential for monitoring DNA damage and repair in human populations has been explored in this review. A systematic search was conducted in PubMed for articles, in English, on human studies reporting γH2AX as a biomarker of either DNA repair or DNA damage. A total of 68 publications were identified. Thirty-four studies (50.0%) evaluated the effect of medical procedures or treatments on γH2AX levels; 20 (29.4%) monitored γH2AX in specific pathological conditions with a case/control or case/case design; 5 studies (7.4%) evaluated the effect of environmental genotoxic exposures, and 9 (13.2%) were descriptive studies on cancer and aging. Peripheral blood lymphocytes (44.6%) or biopsies/tissue specimens (24.3%) were the most commonly used samples. γH2AX was scored by optical microscopy as immunostained foci (78%), or by flow cytometry (16%). Critical features affecting the reliability of the assay, including protocols heterogeneity, specimen, cell cycle, kinetics, study design, and statistical analysis, are hereby discussed. Because of its sensitivity, efficiency and mechanistic relevance, the γH2AX assay has great potential as a DNA damage biomarker; however, the technical and epidemiological heterogeneity highlighted in this review infer a necessity for experimental standardization of the assay.
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Phosphorylated histone H2AX (γH2AX) serves as a biomarker for cellular responses to DNA double-strand breaks.
“Phosphorylated histone H2AX (γH2AX) serves as a biomarker for cellular responses to DSBs, with implications for tracking DNA damage and repair in human populations [33].”
From Celastrol attenuates the invasion and migration and augments the anticancer effects of olaparib in prostate cancer (2024) · cites this paper as [33]
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“Phosphorylated histone H2AX (γH2AX) serves as a biomarker for cellular responses to DSBs, with implications for tracking DNA damage and repair in human populations [33].”
Background
- Authors
- Valdiglesias, V., Giunta, S., Fenech, M., Neri, M., & Bonassi, S.
- Affiliations
- IRCCS San Raffaele Roma (IT)
- Commonwealth Scientific and Industrial Research Organisation (AU)
- Corresponding author
- Bonassi, Stefano
- Venue
- Mutation Research/Reviews in Mutation Research
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 753
- Issue
- 1
- Pages
- 24-40
- ISSN
- 1383-5742 (ISSN-L)
- OpenAlex
- W2060436524
- Cited by
- 277
- References
- 12
- Citations by year
- 2026: 19 · 2025: 26 · 2024: 17 · 2023: 20 · 2022: 19 · 2021: 26 · 2020: 14 · 2019: 20 · 2018: 26 · 2017: 23 · 2016: 21 · 2015: 25 · 2014: 17 · 2013: 4
- FWCI
- 2.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Mutation Research/Reviews in Mutation Research (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- RUC (Universidade Da Coruña) (submittedVersion)
- Funders
- AIRC
- INAIL
- International Cancer Technology Transfer
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Carcinogens and Genotoxicity Assessment
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
- Keywords
- γH2AX, DNA double-strand breaks, genomic instability, DNA damage biomarkers, DNA repair, DNA damage response, peripheral blood lymphocytes, assay standardization, cancer, aging
- MeSH terms
- Animals, Genetics, Population, Histones, Humans, Phosphorylation, Biomarkers, Genomic Instability, DNA Breaks, Double-Stranded
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