The hCOMET project: International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders.
Biomarkers
Comet assay
DNA damage
Human biomonitoring
Pooled analysis
Journal
Mutation research. Reviews in mutation research
ISSN: 1388-2139
Titre abrégé: Mutat Res Rev Mutat Res
Pays: Netherlands
ID NLM: 101632211
Informations de publication
Date de publication:
Historique:
received:
09
05
2020
revised:
25
01
2021
accepted:
27
01
2021
entrez:
4
6
2021
pubmed:
5
6
2021
medline:
23
7
2021
Statut:
ppublish
Résumé
The alkaline comet assay, or single cell gel electrophoresis, is one of the most popular methods for assessing DNA damage in human population. One of the open issues concerning this assay is the identification of those factors that can explain the large inter-individual and inter-laboratory variation. International collaborative initiatives such as the hCOMET project - a COST Action launched in 2016 - represent a valuable tool to meet this challenge. The aims of hCOMET were to establish reference values for the level of DNA damage in humans, to investigate the effect of host factors, lifestyle and exposure to genotoxic agents, and to compare different sources of assay variability. A database of 19,320 subjects was generated, pooling data from 105 studies run by 44 laboratories in 26 countries between 1999 and 2019. A mixed random effect log-linear model, in parallel with a classic meta-analysis, was applied to take into account the extensive heterogeneity of data, due to descriptor, specimen and protocol variability. As a result of this analysis interquartile intervals of DNA strand breaks (which includes alkali-labile sites) were reported for tail intensity, tail length, and tail moment (comet assay descriptors). A small variation by age was reported in some datasets, suggesting higher DNA damage in oldest age-classes, while no effect could be shown for sex or smoking habit, although the lack of data on heavy smokers has still to be considered. Finally, highly significant differences in DNA damage were found for most exposures investigated in specific studies. In conclusion, these data, which confirm that DNA damage measured by the comet assay is an excellent biomarker of exposure in several conditions, may contribute to improving the quality of study design and to the standardization of results of the comet assay in human populations.
Identifiants
pubmed: 34083035
pii: S1383-5742(21)00008-9
doi: 10.1016/j.mrrev.2021.108371
pmc: PMC8525632
mid: NIHMS1739355
pii:
doi:
Substances chimiques
Biomarkers
0
Banques de données
ClinicalTrials.gov
['NCT02231736']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
108371Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors report no declarations of interest.
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