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

被引：55

作者：

Mili, Mirta ^{[1
]}

Ceppi, Marcello ^{[2
]}

Bruzzone, Marco ^{[2
]}

Azqueta, Amaya ^{[3
,4
]}

Brunborg, Gunnar ^{[5
]}

Godschalk, Roger ^{[6
]}

Koppen, Gudrun ^{[7
]}

Langie, Sabine ^{[6
]}

Moller, Peter ^{[8
]}

Teixeira, Joao Paulo ^{[9
,60
]}

Alija, Avdulla ^{[10
]}

Anderson, Diana ^{[11
]}

Andrade, Vanessa ^{[12
]}

Andreoli, Cristina ^{[13
]}

Asllani, Fisnik ^{[10
]}

Bangkoglu, Ezgi Eyluel ^{[14
]}

Barancokova, Magdalena ^{[15
]}

Basaran, Nursen ^{[16
]}

Boutet-Robinet, Elisa ^{[17
]}

Buschini, Annamaria ^{[18
]}

Cavallo, Delia ^{[19
]}

Pereira, Cristiana Costa ^{[9
,60
]}

Costa, Carla ^{[9
,60
]}

Costa, Solange ^{[9
,60
]}

Silva, Juliana Da ^{[20
]}

Bo, Cristian Del ^{[21
]}

Sreckovic, Vesna Dimitrijevic ^{[22
]}

Djelic, Ninoslav ^{[23
]}

Durackova, Zdenka ^{[24
]}

Dvorakova, Monika ^{[25
]}

Gajski, Goran ^{[1
]}

Galati, Serena ^{[26
]}

Lima, Omar Garcia ^{[27
]}

Giovannelli, Lisa ^{[28
]}

Goroshinskaya, Irina A. ^{[29
]}

Grindel, Annemarie ^{[30
]}

Gutzkow, Kristine B. ^{[5
]}

Hernandez, Alba ^{[31
,32
]}

Hernandez, Carlos ^{[33
]}

Holven, Kirsten B. ^{[34
]}

Ibero-Baraibar, Idoia ^{[35
]}

Ottestad, Inger ^{[34
]}

Kadioglu, Ela ^{[36
]}

Kazimirova, Alena ^{[15
]}

Kuznetsova, Elena ^{[37
]}

Ladeira, Carina ^{[35
,38
]}

Laffon, Blanca ^{[39
]}

Lamonaca, Palma ^{[40
]}

Lebailly, Pierre ^{[41
,42
]}

Louro, Henriqueta ^{[43
,44
]}

机构：

[1] Inst Med Res & Occupat Hlth, Mutagenesis Unit, Ksaverska Cesta 2, Zagreb 10000, Croatia

[2] San Martino Policlin Hosp, Biostat Unit, Genoa, Italy

[3] Univ Navarra, Dept Pharmacol & Toxicol, C Irunlarrea 1, Pamplona 31008, Spain

[4] Navarra Inst Hlth Res, IdiSNA, C Irunlarrea 3, Pamplona 31008, Spain

[5] Norwegian Inst Publ Hlth NIPH, Sect Mol Toxicol, Dept Environm Hlth, Lovisenberggt 6, N-0456 Oslo, Norway

[6] Univ Maastricht, Sch Nutr & Translat Res Metab, Dept Pharmacol & Toxicol, Univ Singel 50, NL-6200 MD Maastricht, Netherlands

[7] Flemish Inst Technol Res, Environm Risk & Hlth Unit VITO BIOMo, Antwerp, Belgium

[8] Univ Copenhagen, Sect Environm Hlth, Dept Publ Hlth, Oster Farimagsgade 5A, DK-1014 Copenhagen, Denmark

[9] Natl Inst Hlth Dr Ricardo Jorge, Environm Hlth Dept, Rua Alexandre Herculano 321, P-4000055 Porto, Portugal

[10] Univ Prishtina, Dept Biol, Prishtina 10000, Kosovo

[11] Univ Bradford, Biomed Sci Dept, Richmond Rd Bradford, Bradford BD7 1DP, W Yorkshire, England

[12] Univ Southern Santa Catarina, UNESC, Lab Translat Biomed, Criciuma, SC, Brazil

[13] Ist Super Sanita, Dept Environm & Hlth, Viale Regina Elena 299, Rome, Italy

[14] Univ Wurzburg, Inst Pharmacol & Toxicol, VersbacherStr 9, D-97078 Wurzburg, Germany

[15] Slovak Med Univ, Inst Biol, Med Fac, Limbova 12, Bratislava 83303, Slovakia

[16] Hacettepe Univ, Dept Pharmaceut Toxicol, Fac Pharm, Ankara, Turkey

[17] Univ Toulouse, Toxalim Res Ctr Food Toxicol, INRAE, ENVT,INP Purpan,UPS, Toulouse, France

[18] Univ Parma, Dept Chem Life Sci & Environm Sustainabil, Parco Area Sci 11A, I-43124 Parma, Italy

[19] Italian Workers Compensat Author INAIL, Dept Occupat & Environm Med, Epidemiol & Hyg DiMEILA, Via Fontana Candida 1, I-00078 Rome, Italy

[20] Lutheran Univ Brazil ULBRA, Lab Genet Toxicol, Av Farroupilha 8001,Predio 22-Sala 22, BR-92425900 Canoas, RS, Brazil

[21] Univ Milan, Dept Food Environm & Nutr Sci DeFENS, Via Celoria 2, I-20133 Milan, Italy

[22] Univ Belgrade, Clin Endocrinol Diabet & Metab Dis, Fac Med, Dr Subot 13, Belgrade, Serbia

[23] Univ Belgrade, Dept Biol, Fac Vet Med, Oslobodjenja Blvd 18, Belgrade 11000, Serbia

[24] Natl Inst Hyg, Natl Inst Publ Hlth, Dept Radiat Hyg & Radiobiol, 24 Chocimska St, PL-00791 Warsaw, Poland

[25] Comenius Univ, Inst Med Chem Biochem & Clin Biochem, Fac Med, Sasinkova 2, Bratislava, Slovakia

[26] Univ Parma, Ctr Mol & Translat Oncol, Parco Area Sci 11A, I-43124 Parma, Italy

[27] Ctr RadiationProtect & Hyg, Calle 20,4113,e-41 & 47 Playa CP 11300,AP 6195, Havana 10600, Habana, Cuba

[28] Univ Florence, Dept NEUROFARBA, Viale G Pieraccini 6, I-50139 Florence, Italy

[29] Natl Med Res Ctr Oncol, Lab Study Pathogenesis Malignant Tumors, 14 Line 63, Rostov Na Donu 344037, Russia

[30] Univ Vienna, Dept Nutr Sci, Althanstr 14, A-1090 Vienna, Austria

[31] Univ Autonoma Barcelona, Fac Biosci, Dept Genet & Microbiol, Cerdanyola Del Valles 08193, Barcelona, Spain

[32] Carlos III Inst Hlth, Consortium Biomed Res Epidemiol & Publ Hlth CIBER, Madrid 28029, Spain

[33] Inst Ciencias Basicas & Preclin Victoria Giron, Dept Biochem, 146 St & 31 Ave,3102, Playa, Habana, Cuba

[34] Univ Oslo, Inst Basic Med Sci, Dept Nutr, Sognsvannsveien 9, N-0372 Oslo, Norway

[35] Univ Navarra, Dept Nutr Food Sci & Physiol, Ctr Nutr Res, Irunlarrea 1, Navarra 31008, Spain

[36] Gazi Univ, Toxicol Dept, Fac Pharm, Ankara, Turkey

[37] Russian Acad Sci, Inst Theoret & Expt Biophys, Inst Skaya 3, Pushchino 142290, Moscow Region, Russia

[38] Univ Nova Lisboa, NOVA Natl Sch Publ Hlth, Publ Hlth Res Ctr, Lisbon, Portugal

[39] Univ A Coruna, Ctr Invest Cient Avanzadas CICA, Fac Ciencias Educ, Grp DICOMOSA,Dept Psicol, Campus Elvina S-N, La Coruna 15071, Spain

[40] San Raffaele Univ, Dept Human Sci & Qual Life Promot, Unit Clin & Mol Epidemiol, IRCCS San Raffaele Pisana, Via Val Cannuta 247, I-00161 Rome, Italy

[41] INSERM, ANTICIPE Unit, Ave Gen Harris, F-14076 Caen 05, France

[42] Univ Caen, Normandie Ctr Francois Baclesse, Ave Gen Harris, F-14076 Caen 05, France

[43] Natl Inst Hlth Doutor Ricardo Jorge, Human Genet Dept, Av Padre Cruz, P-1649016 Lisbon, Portugal

[44] NOVA Univ Lisbon, ToxOm, NMS, Lisbon, Portugal

[45] Univ Perugia, Dept Pharmaceut Sci, Unit Publ Hlth, Via Giochetto, I-06122 Perugia, Italy

[46] Univ Florence, Palagi Hosp, Div Dermatol, Dept Hlth Sci, Viale Michelangelo 41, Florence, Italy

[47] Natl Publ Hlth Ctr, Dept Nonionizing Radiat, Anna St 5, H-1221 Budapest, Hungary

[48] Czech Acad Sci, Inst Expt Med, Dept Nanotoxicolgy & Mol Epidemiol, Videnska 1083, Prague, Czech Republic

[49] Mem Sloan Kettering Canc Ctr, Epidemiol & Biostat, New York, NY 10065 USA

[50] Univ Paris Saclay, CESP, Villejuif, France

来源：

MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH | 2021年 / 787卷

关键词：

Comet assay; DNA damage; Pooled analysis; Human biomonitoring; Biomarkers; HUMAN MICRONUCLEUS PROJECT; HUMAN-LYMPHOCYTES; POOLED ANALYSIS; HOST FACTORS; CELLS; SMOKING;

D O I：

10.1016/j.mrrev.2021.108371

中图分类号：

Q81 [生物工程学（生物技术）]; Q93 [微生物学];

学科分类号：

071005 ; 0836 ; 090102 ; 100705 ;

摘要：

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/).

引用

页数：13

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