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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.
Mutation Research/Reviews in Mutation Research ( IF 5.3 ) Pub Date : 2021-02-06 , DOI: 10.1016/j.mrrev.2021.108371
Mirta Milić 1 , Marcello Ceppi 2 , Marco Bruzzone 2 , Amaya Azqueta 3 , Gunnar Brunborg 4 , Roger Godschalk 5 , Gudrun Koppen 6 , Sabine Langie 5 , Peter Møller 7 , João Paulo Teixeira 8 , Avdulla Alija 9 , Diana Anderson 10 , Vanessa Andrade 11 , Cristina Andreoli 12 , Fisnik Asllani 9 , Ezgi Eyluel Bangkoglu 13 , Magdalena Barančoková 14 , Nursen Basaran 15 , Elisa Boutet-Robinet 16 , Annamaria Buschini 17 , Delia Cavallo 18 , Cristiana Costa Pereira 8 , Carla Costa 8 , Solange Costa 8 , Juliana Da Silva 19 , Cristian Del Boˊ 20 , Vesna Dimitrijević Srećković 21 , Ninoslav Djelić 22 , Malgorzata Dobrzyńska 23 , Zdenka Duračková 24 , Monika Dvořáková 24 , Goran Gajski 1 , Serena Galati 25 , Omar García Lima 26 , Lisa Giovannelli 27 , Irina A Goroshinskaya 28 , Annemarie Grindel 29 , Kristine B Gutzkow 4 , Alba Hernández 30 , Carlos Hernández 31 , Kirsten B Holven 32 , Idoia Ibero-Baraibar 33 , Inger Ottestad 32 , Ela Kadioglu 34 , Alena Kažimirová 14 , Elena Kuznetsova 35 , Carina Ladeira 36 , Blanca Laffon 37 , Palma Lamonaca 38 , Pierre Lebailly 39 , Henriqueta Louro 40 , Tania Mandina Cardoso 26 , Francesca Marcon 12 , Ricard Marcos 30 , Massimo Moretti 41 , Silvia Moretti 42 , Mojgan Najafzadeh 10 , Zsuzsanna Nemeth 43 , Monica Neri 38 , Bozena Novotna 44 , Irene Orlow 45 , Zuzana Paduchova 24 , Susana Pastor 30 , Hervé Perdry 46 , Biljana Spremo-Potparević 47 , Dwi Ramadhani 48 , Patrizia Riso 20 , Paula Rohr 11 , Emilio Rojas 49 , Pavel Rossner 44 , Anna Safar 43 , Semra Sardas 50 , Maria João Silva 40 , Nikolay Sirota 35 , Bozena Smolkova 51 , Marta Staruchova 14 , Rudolf Stetina 52 , Helga Stopper 13 , Ekaterina I Surikova 28 , Stine M Ulven 32 , Cinzia Lucia Ursini 18 , Vanessa Valdiglesias 53 , Mahara Valverde 49 , Pavel Vodicka 54 , Katarina Volkovova 14 , Karl-Heinz Wagner 29 , Lada Živković 47 , Maria Dušinská 55 , Andrew R Collins 32 , Stefano Bonassi 38
Affiliation  

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.

中文翻译:

hCOMET 项目:人类生物监测中彗星试验结果的国际数据库比较。DNA 损伤的基线频率和主要混杂因素的影响。

碱性彗星试验或单细胞凝胶电泳是评估人群 DNA 损伤的最常用方法之一。与该测定有关的未决问题之一是确定那些可以解释个体间和实验室间差异的因素。hCOMET 项目(2016 年启动的 COST 行动)等国际合作倡议是应对这一挑战的宝贵工具。hCOMET 的目的是建立人类 DNA 损伤水平的参考值,研究宿主因素、生活方式和接触遗传毒性物质的影响,并比较不同的测定变异来源。生成了一个包含 19,320 名受试者的数据库,汇集了 1999 年至 2019 年间由 26 个国家/地区的 44 个实验室进行的 105 项研究的数据。应用混合随机效应对数线性模型与经典荟萃分析并行,以考虑由于描述符、样本和协议可变性而导致的数据的广泛异质性。作为这种分析的结果,DNA 链断裂的四分位间距(包括碱不稳定位点)报告了尾强度、尾长和尾矩(彗星测定描述符)。在一些数据集中报告了年龄的小变化,表明在最老的年龄组中 DNA 损伤较高,而对性别或吸烟习惯没有影响,尽管仍然需要考虑缺乏重度吸烟者的数据。最后,在特定研究中调查的大多数暴露中发现 DNA 损伤具有非常显着的差异。总之,这些数据,
更新日期:2021-02-06
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