γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies

Vanessa Valdiglesias, Simona Giunta, Michael Fenech, Monica Neri, Stefano Bonassi

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)24-40
Number of pages17
JournalMutation Research - Reviews in Mutation Research
Volume753
Issue number1
DOIs
Publication statusPublished - Jul 2013

Fingerprint

Double-Stranded DNA Breaks
Genomic Instability
DNA Damage
Population
Biomarkers
DNA Repair
Environmental Exposure
Eukaryotic Cells
PubMed
Histones
Publications
Microscopy
Cell Cycle
Flow Cytometry
Carcinogenesis
Lymphocytes
Biopsy
Neoplasms

Keywords

  • γH2AX
  • DNA double strand breaks
  • Genomic instability
  • Human population studies
  • Molecular epidemiology

ASJC Scopus subject areas

  • Genetics
  • Health, Toxicology and Mutagenesis

Cite this

γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies. / Valdiglesias, Vanessa; Giunta, Simona; Fenech, Michael; Neri, Monica; Bonassi, Stefano.

In: Mutation Research - Reviews in Mutation Research, Vol. 753, No. 1, 07.2013, p. 24-40.

Research output: Contribution to journalArticle

@article{f3841a555d0c4dba999ea5ae3d2652ef,
title = "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.",
keywords = "γH2AX, DNA double strand breaks, Genomic instability, Human population studies, Molecular epidemiology",
author = "Vanessa Valdiglesias and Simona Giunta and Michael Fenech and Monica Neri and Stefano Bonassi",
year = "2013",
month = "7",
doi = "10.1016/j.mrrev.2013.02.001",
language = "English",
volume = "753",
pages = "24--40",
journal = "Mutation Research - Reviews in Mutation Research",
issn = "1383-5742",
publisher = "Elsevier B.V.",
number = "1",

}

TY - JOUR

T1 - γH2AX as a marker of DNA double strand breaks and genomic instability in human population studies

AU - Valdiglesias, Vanessa

AU - Giunta, Simona

AU - Fenech, Michael

AU - Neri, Monica

AU - Bonassi, Stefano

PY - 2013/7

Y1 - 2013/7

N2 - 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.

AB - 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.

KW - γH2AX

KW - DNA double strand breaks

KW - Genomic instability

KW - Human population studies

KW - Molecular epidemiology

UR - http://www.scopus.com/inward/record.url?scp=84881243042&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881243042&partnerID=8YFLogxK

U2 - 10.1016/j.mrrev.2013.02.001

DO - 10.1016/j.mrrev.2013.02.001

M3 - Article

C2 - 23416207

AN - SCOPUS:84881243042

VL - 753

SP - 24

EP - 40

JO - Mutation Research - Reviews in Mutation Research

JF - Mutation Research - Reviews in Mutation Research

SN - 1383-5742

IS - 1

ER -