TY - JOUR

T1 - The hCOMET project

T2 - International database comparison of results with the comet assay in human biomonitoring. Baseline frequency of DNA damage and effect of main confounders

AU - Mili, Mirta

AU - Ceppi, Marcello

AU - Bruzzone, Marco

AU - Azqueta, Amaya

AU - Brunborg, Gunnar

AU - Godschalk, Roger

AU - Koppen, Gudrun

AU - Langie, Sabine

AU - Møller, Peter

AU - Teixeira, Joao Paulo

AU - Alija, Avdulla

AU - Anderson, Diana

AU - Andrade, Vanessa

AU - Andreoli, Cristina

AU - Asllani, Fisnik

AU - Bangkoglu, Ezgi Eyluel

AU - Barancokova, Magdalena

AU - Basaran, Nursen

AU - Boutet-Robinet, Elisa

AU - Buschini, Annamaria

AU - Cavallo, Delia

AU - Pereira, Cristiana Costa

AU - Costa, Carla

AU - Costa, Solange

AU - Silva, Juliana Da

AU - Bo, Cristian Del

AU - Sreckovic, Vesna Dimitrijevic

AU - Djelic, Ninoslav

AU - Durackova, Zdenka

AU - Dvorakova, Monika

AU - Gajski, Goran

AU - Galati, Serena

AU - Lima, Omar Garcia

AU - Giovannelli, Lisa

AU - Goroshinskaya, Irina A.

AU - Grindel, Annemarie

AU - Gutzkow, Kristine B.

AU - Hernandez, Alba

AU - Hernandez, Carlos

AU - Holven, Kirsten B.

AU - Ibero-Baraibar, Idoia

AU - Ottestad, Inger

AU - Kadioglu, Ela

AU - Kazimirova, Alena

AU - Kuznetsova, Elena

AU - Ladeira, Carina

AU - Laffon, Blanca

AU - Lamonaca, Palma

AU - Lebailly, Pierre

AU - Louro, Henriqueta

AU - Cardoso, Tania Mandina

AU - Marcon, Francesca

AU - Marcos, Ricard

AU - Moretti, Massimo

AU - Moretti, Silvia

AU - Najafzadeh, Mojgan

AU - Nemeth, Zsuzsanna

AU - Neri, Monica

AU - Novotna, Bozena

AU - Orlow, Irene

AU - Paduchova, Zuzana

AU - Pastor, Susana

AU - Perdry, Herve

AU - Spremo-Potparevic, Biljana

AU - Ramadhani, Dwi

AU - Riso, Patrizia

AU - Rohr, Paula

AU - Rojas, Emilio

AU - Rossner, Pavel

AU - Safar, Anna

AU - Sardas, Semra

AU - Silva, Maria Joao

AU - Sirota, Nikolay

AU - Smolkova, Bozena

AU - Staruchova, Marta

AU - Stetina, Rudolf

AU - Stopper, Helga

AU - Surikova, Ekaterina I.

AU - Ulven, Stine M.

AU - Ursini, Cinzia Lucia

AU - Valdiglesias, Vanessa

AU - Valverde, Mahara

AU - Vodicka, Pavel

AU - Volkovova, Katarina

AU - Wagner, Karl-Heinz

AU - Zivkovic, Lada

AU - Dusinska, Maria

AU - Collins, Andrew R.

AU - Bonassi, Stefano

PY - 2021

Y1 - 2021

N2 - 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.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

AB - 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.(c) 2021 The Authors. Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

KW - Comet assay

KW - DNA damage

KW - Pooled analysis

KW - Human biomonitoring

KW - Biomarkers

KW - HUMAN MICRONUCLEUS PROJECT

KW - HUMAN-LYMPHOCYTES

KW - POOLED ANALYSIS

KW - HOST FACTORS

KW - CELLS

KW - SMOKING

U2 - 10.1016/j.mrrev.2021.108371

DO - 10.1016/j.mrrev.2021.108371

M3 - Review

C2 - 34083035

VL - 787

JO - Mutation Research - Reviews

JF - Mutation Research - Reviews

SN - 1383-5742

M1 - 108371

ER -