Levels of DNA damage represent the dynamics between damage formation and removal. Therefore, to better interpret human biomonitoring studies with DNA damage endpoints, an individual's ability to recognize and properly remove DNA damage should be characterized. Relatively few studies have included DNA repair as a biomarker and therefore, assembling and analyzing a pooled database of studies with data on base excision repair (BER) was one of the goals of hCOMET (EU-COST CA15132). A group of approximately 1911 individuals, was gathered from 8 laboratories which run population studies with the comet-based in vitro DNA repair assay. BER incision activity data were normalized and subsequently correlated with various host factors. BER was found to be significantly higher in women. Although it is generally accepted that age is inversely related to DNA repair, no overall effect of age was found, but sex differences were most pronounced in the oldest quartile (>61 years). No effect of smoking or occupational exposures was found. A body mass index (BMI) above 25 kg/m2 was related to higher levels of BER. However, when BMI exceeded 35 kg/m2, repair incision activity was significantly lower. Finally, higher BER incision activity was related to lower levels of DNA damage detected by the comet assay in combination with formamidopyrimidine DNA glycosylase (Fpg), which is in line with the fact that oxidatively damaged DNA is repaired by BER. These data indicate that BER plays a role in modulating the steady-state level of DNA damage that is detected in molecular epidemiological studies and should therefore be considered as a parallel endpoint in future studies.
- MeSH
- DNA-formamidopyrimidinglykosylasa MeSH
- epidemiologické studie MeSH
- kometový test MeSH
- lidé středního věku MeSH
- lidé MeSH
- oprava DNA * genetika MeSH
- poškození DNA * MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
The comet assay is a widely used test for the detection of DNA damage and repair activity. However, there are interlaboratory differences in reported levels of baseline and induced damage in the same experimental systems. These differences may be attributed to protocol differences, although it is difficult to identify the relevant conditions because detailed comet assay procedures are not always published. Here, we present a Consensus Statement for the Minimum Information for Reporting Comet Assay (MIRCA) providing recommendations for describing comet assay conditions and results. These recommendations differentiate between 'desirable' and 'essential' information: 'essential' information refers to the precise details that are necessary to assess the quality of the experimental work, whereas 'desirable' information relates to technical issues that might be encountered when repeating the experiments. Adherence to MIRCA recommendations should ensure that comet assay results can be easily interpreted and independently verified by other researchers.
- MeSH
- dodržování směrnic statistika a číselné údaje MeSH
- kometový test metody normy MeSH
- konsensus MeSH
- laboratoře MeSH
- lidé MeSH
- výzkumný projekt * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
BACKGROUND/AIM: Biomonitoring is currently applied in the estimation of health risks after overexposure to ionizing radiation (IR). The aim of this study was to compare the association of dicentric chromosomes and acentric fragments (AF) with cancer risk in subjects exposed to IR, as well as in control subjects. MATERIALS AND METHODS: The study was performed on 3,574 subjects (2,030 subjects exposed to IR and 1,544 control subjects). The mean follow-up period was 8 years. RESULTS: In subjects reporting exposure to IR, the presence of AFs and dicentric chromosomes was associated with a significant increase in cancer risk, hazard ratio (HR)=1.78 (95% confidence interval (CI)=1.01-3.13) and HR=1.73 (95% CI=1.03-2.90), respectively. CONCLUSION: AFs are associated with cancer risk and have a similar sensitivity to dicentric chromosomes in subjects exposed to IR. Because automated AF scoring can be easily introduced using fast flow cytometry combined with the pan-centromere staining, this biomarker may hold promise as a potential sensitive biomarker of exposure to IR and cancer risk.
- MeSH
- chromozomální aberace * MeSH
- genetická predispozice k nemoci * MeSH
- ionizující záření * MeSH
- lidé MeSH
- nádory vyvolané zářením genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
