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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

Mirta Milić 1 Marcello Ceppi 2 Marco Bruzzone 2 Amaya Azqueta 3, 4 Gunnar Brunborg 5 Roger Godschalk 6 Gudrun Koppen 7 Sabine Langie 6 Peter Møller 8 João Paulo Teixeira 9, 2, 8 Avdulla Alija 10 Diana Anderson 11 Vanessa Andrade 12 Cristina Andreoli 13 Fisnik Asllani 10 Ezgi Eyluel Bangkoglu 14 Magdalena Barančoková 15 Nursen Basaran 16 Elisa Boutet-Robinet 17 Annamaria Buschini 18 Delia Cavallo 19 Cristiana Costa Pereira 9, 2, 8 Carla Costa 9, 2, 8 Solange Costa 9, 2, 8 Juliana da Silva 20 Cristian del Boˊ 21 Vesna Dimitrijević Srećković 22 Ninoslav Djelić 23 Malgorzata Dobrzyńska 24 Zdenka Duračková 25 Monika Dvořáková 25 Goran Gajski 1 Serena Galati 26 Omar García Lima 27 Lisa Giovannelli 28 Irina Goroshinskaya 29 Annemarie Grindel 30 Kristine Gutzkow 5 Alba Hernández 31, 32 Carlos Hernández 33 Kirsten Holven 34 Idoia Ibero-Baraibar 3 Inger Ottestad 34 Ela Kadioglu 35 Alena Kažimirová 15 Elena Kuznetsova 36 Carina Ladeira 37, 38 Blanca Laffon 39 Palma Lamonaca 40 Pierre Lebailly 41 Henriqueta Louro 38 Tania Mandina Cardoso 27 Francesca Marcon 13 Ricard Marcos 31, 32 Massimo Moretti 42 Silvia Moretti 43 Mojgan Najafzadeh 8 Zsuzsanna Nemeth 44 Monica Neri 45 Bozena Novotna 46 Irene Orlow 47 Zuzana Paduchova 25 Susana Pastor 31, 32 Hervé Perdry 48 Biljana Spremo-Potparević 49 Dwi Ramadhani 50 Patrizia Riso 21 Paula Rohr 12 Emilio Rojas 51 Pavel Rossner 46 Anna Safar 44 Semra Sardas 52 Maria João Silva 38 Nikolay Sirota 53 Bozena Smolkova 54 Marta Staruchova 15 Rudolf Stetina 55 Helga Stopper 14 Ekaterina Surikova 29 Stine Ulven 34 Cinzia Lucia Ursini 56 Vanessa Valdiglesias 57 Mahara Valverde 51 Pavel Vodicka 58 Katarina Volkovova 15 Karl-Heinz Wagner 30 Lada Živković 59 Maria Dušinská 60 Andrew Collins 34 Stefano Bonassi 45
Abstract : 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.
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Submitted on : Wednesday, March 10, 2021 - 12:31:39 PM
Last modification on : Wednesday, June 16, 2021 - 2:22:01 PM

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Mirta Milić, Marcello Ceppi, Marco Bruzzone, Amaya Azqueta, Gunnar Brunborg, et al.. 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. Mutation Research - Reviews, Elsevier, 2021, 787, pp.108371. ⟨10.1016/j.mrrev.2021.108371⟩. ⟨hal-03164976⟩

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