¦ÃH2AX as a marker of DNA double strand breaks and genomic instability in human population studies
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- 作者：Vanessa Valdiglesias ; Simona Giunta ; Michael Fenech ; Monica Neri ; Stefano Bonassi
- 关键词：¦ÃH2AX ; DNA double strand breaks ; Genomic instability ; Human population studies ; Molecular epidemiology
- 刊名：Mutation Research/Reviews in Mutation Research
- 出版年：2013
- 出版时间：July-September, 2013
- 年：2013
- 卷：753
- 期：1
- 页码：24-40
- 全文大小：1066 K
文摘
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 (¦ÃH2AX) 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 ¦ÃH2AX 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 ¦ÃH2AX levels; 20 (29.4 % ) monitored ¦ÃH2AX 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. ¦ÃH2AX 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 ¦ÃH2AX 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.