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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
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, sp...ecimen 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.
Keywords:
DNA damage / Biomarkers / Comet assay / Human biomonitoring / Pooled analysis
Source:
Mutation Research - Reviews in Mutation Research, 2021, 787
TY - JOUR
AU - Milić, 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, João Paulo
AU - Alija, Avdulla
AU - Anderson, Diana
AU - Andrade, Vanessa
AU - Andreoli, Cristina
AU - Asllani, Fisnik
AU - Bangkoglu, Ezgi Eyluel
AU - Barančoková, Magdalena
AU - Basaran, Nursen
AU - Boutet-Robinet, Elisa
AU - Buschini, Annamaria
AU - Cavallo, Delia
AU - Costa Pereira, Cristiana
AU - Costa, Carla
AU - Costa, Solange
AU - Da Silva, Juliana
AU - Del Boˊ, Cristian
AU - Dimitrijević Srećković, Vesna
AU - Đelić, Ninoslav
AU - Dobrzyńska, Malgorzata
AU - Duračková, Zdenka
AU - Dvořáková, Monika
AU - Gajski, Goran
AU - Galati, Serena
AU - García Lima, Omar
AU - Giovannelli, Lisa
AU - Goroshinskaya, Irina A.
AU - Grindel, Annemarie
AU - Gutzkow, Kristine B.
AU - Hernández, Alba
AU - Hernández, Carlos
AU - Holven, Kirsten B.
AU - Ibero-Baraibar, Idoia
AU - Ottestad, Inger
AU - Kadioglu, Ela
AU - Kažimirová, Alena
AU - Kuznetsova, Elena
AU - Ladeira, Carina
AU - Laffon, Blanca
AU - Lamonaca, Palma
AU - Lebailly, Pierre
AU - Louro, Henriqueta
AU - Mandina Cardoso, Tania
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, Hervé
AU - Spremo-Potparević, 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 João
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 - Živković, Lada
AU - Dušinská, Maria
AU - Collins, Andrew R.
AU - Bonassi, Stefano
PY - 2021
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3791
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.
PB - Elsevier B.V.
T2 - Mutation Research - Reviews in Mutation Research
T1 - 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
VL - 787
DO - 10.1016/j.mrrev.2021.108371
ER -
@article{
author = "Milić, Mirta and Ceppi, Marcello and Bruzzone, Marco and Azqueta, Amaya and Brunborg, Gunnar and Godschalk, Roger and Koppen, Gudrun and Langie, Sabine and Møller, Peter and Teixeira, João Paulo and Alija, Avdulla and Anderson, Diana and Andrade, Vanessa and Andreoli, Cristina and Asllani, Fisnik and Bangkoglu, Ezgi Eyluel and Barančoková, Magdalena and Basaran, Nursen and Boutet-Robinet, Elisa and Buschini, Annamaria and Cavallo, Delia and Costa Pereira, Cristiana and Costa, Carla and Costa, Solange and Da Silva, Juliana and Del Boˊ, Cristian and Dimitrijević Srećković, Vesna and Đelić, Ninoslav and Dobrzyńska, Malgorzata and Duračková, Zdenka and Dvořáková, Monika and Gajski, Goran and Galati, Serena and García Lima, Omar and Giovannelli, Lisa and Goroshinskaya, Irina A. and Grindel, Annemarie and Gutzkow, Kristine B. and Hernández, Alba and Hernández, Carlos and Holven, Kirsten B. and Ibero-Baraibar, Idoia and Ottestad, Inger and Kadioglu, Ela and Kažimirová, Alena and Kuznetsova, Elena and Ladeira, Carina and Laffon, Blanca and Lamonaca, Palma and Lebailly, Pierre and Louro, Henriqueta and Mandina Cardoso, Tania and Marcon, Francesca and Marcos, Ricard and Moretti, Massimo and Moretti, Silvia and Najafzadeh, Mojgan and Nemeth, Zsuzsanna and Neri, Monica and Novotna, Bozena and Orlow, Irene and Paduchova, Zuzana and Pastor, Susana and Perdry, Hervé and Spremo-Potparević, Biljana and Ramadhani, Dwi and Riso, Patrizia and Rohr, Paula and Rojas, Emilio and Rossner, Pavel and Safar, Anna and Sardas, Semra and Silva, Maria João and Sirota, Nikolay and Smolkova, Bozena and Staruchova, Marta and Stetina, Rudolf and Stopper, Helga and Surikova, Ekaterina I. and Ulven, Stine M. and Ursini, Cinzia Lucia and Valdiglesias, Vanessa and Valverde, Mahara and Vodicka, Pavel and Volkovova, Katarina and Wagner, Karl-Heinz and Živković, Lada and Dušinská, Maria and Collins, Andrew R. and Bonassi, Stefano",
year = "2021",
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.",
publisher = "Elsevier B.V.",
journal = "Mutation Research - Reviews in Mutation Research",
title = "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",
volume = "787",
doi = "10.1016/j.mrrev.2021.108371"
}
Milić, M., Ceppi, M., Bruzzone, M., Azqueta, A., Brunborg, G., Godschalk, R., Koppen, G., Langie, S., Møller, P., Teixeira, J. P., Alija, A., Anderson, D., Andrade, V., Andreoli, C., Asllani, F., Bangkoglu, E. E., Barančoková, M., Basaran, N., Boutet-Robinet, E., Buschini, A., Cavallo, D., Costa Pereira, C., Costa, C., Costa, S., Da Silva, J., Del Boˊ, C., Dimitrijević Srećković, V., Đelić, N., Dobrzyńska, M., Duračková, Z., Dvořáková, M., Gajski, G., Galati, S., García Lima, O., Giovannelli, L., Goroshinskaya, I. A., Grindel, A., Gutzkow, K. B., Hernández, A., Hernández, C., Holven, K. B., Ibero-Baraibar, I., Ottestad, I., Kadioglu, E., Kažimirová, A., Kuznetsova, E., Ladeira, C., Laffon, B., Lamonaca, P., Lebailly, P., Louro, H., Mandina Cardoso, T., Marcon, F., Marcos, R., Moretti, M., Moretti, S., Najafzadeh, M., Nemeth, Z., Neri, M., Novotna, B., Orlow, I., Paduchova, Z., Pastor, S., Perdry, H., Spremo-Potparević, B., Ramadhani, D., Riso, P., Rohr, P., Rojas, E., Rossner, P., Safar, A., Sardas, S., Silva, M. J., Sirota, N., Smolkova, B., Staruchova, M., Stetina, R., Stopper, H., Surikova, E. I., Ulven, S. M., Ursini, C. L., Valdiglesias, V., Valverde, M., Vodicka, P., Volkovova, K., Wagner, K., Živković, L., Dušinská, M., Collins, A. R.,& Bonassi, S.. (2021). 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. in Mutation Research - Reviews in Mutation Research
Elsevier B.V.., 787.
https://doi.org/10.1016/j.mrrev.2021.108371
Milić M, Ceppi M, Bruzzone M, Azqueta A, Brunborg G, Godschalk R, Koppen G, Langie S, Møller P, Teixeira JP, Alija A, Anderson D, Andrade V, Andreoli C, Asllani F, Bangkoglu EE, Barančoková M, Basaran N, Boutet-Robinet E, Buschini A, Cavallo D, Costa Pereira C, Costa C, Costa S, Da Silva J, Del Boˊ C, Dimitrijević Srećković V, Đelić N, Dobrzyńska M, Duračková Z, Dvořáková M, Gajski G, Galati S, García Lima O, Giovannelli L, Goroshinskaya IA, Grindel A, Gutzkow KB, Hernández A, Hernández C, Holven KB, Ibero-Baraibar I, Ottestad I, Kadioglu E, Kažimirová A, Kuznetsova E, Ladeira C, Laffon B, Lamonaca P, Lebailly P, Louro H, Mandina Cardoso T, Marcon F, Marcos R, Moretti M, Moretti S, Najafzadeh M, Nemeth Z, Neri M, Novotna B, Orlow I, Paduchova Z, Pastor S, Perdry H, Spremo-Potparević B, Ramadhani D, Riso P, Rohr P, Rojas E, Rossner P, Safar A, Sardas S, Silva MJ, Sirota N, Smolkova B, Staruchova M, Stetina R, Stopper H, Surikova EI, Ulven SM, Ursini CL, Valdiglesias V, Valverde M, Vodicka P, Volkovova K, Wagner K, Živković L, Dušinská M, Collins AR, Bonassi S. 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. in Mutation Research - Reviews in Mutation Research. 2021;787.
doi:10.1016/j.mrrev.2021.108371 .
Milić, Mirta, Ceppi, Marcello, Bruzzone, Marco, Azqueta, Amaya, Brunborg, Gunnar, Godschalk, Roger, Koppen, Gudrun, Langie, Sabine, Møller, Peter, Teixeira, João Paulo, Alija, Avdulla, Anderson, Diana, Andrade, Vanessa, Andreoli, Cristina, Asllani, Fisnik, Bangkoglu, Ezgi Eyluel, Barančoková, Magdalena, Basaran, Nursen, Boutet-Robinet, Elisa, Buschini, Annamaria, Cavallo, Delia, Costa Pereira, Cristiana, Costa, Carla, Costa, Solange, Da Silva, Juliana, Del Boˊ, Cristian, Dimitrijević Srećković, Vesna, Đelić, Ninoslav, Dobrzyńska, Malgorzata, Duračková, Zdenka, Dvořáková, Monika, Gajski, Goran, Galati, Serena, García Lima, Omar, Giovannelli, Lisa, Goroshinskaya, Irina A., Grindel, Annemarie, Gutzkow, Kristine B., Hernández, Alba, Hernández, Carlos, Holven, Kirsten B., Ibero-Baraibar, Idoia, Ottestad, Inger, Kadioglu, Ela, Kažimirová, Alena, Kuznetsova, Elena, Ladeira, Carina, Laffon, Blanca, Lamonaca, Palma, Lebailly, Pierre, Louro, Henriqueta, Mandina Cardoso, Tania, Marcon, Francesca, Marcos, Ricard, Moretti, Massimo, Moretti, Silvia, Najafzadeh, Mojgan, Nemeth, Zsuzsanna, Neri, Monica, Novotna, Bozena, Orlow, Irene, Paduchova, Zuzana, Pastor, Susana, Perdry, Hervé, Spremo-Potparević, Biljana, Ramadhani, Dwi, Riso, Patrizia, Rohr, Paula, Rojas, Emilio, Rossner, Pavel, Safar, Anna, Sardas, Semra, Silva, Maria João, Sirota, Nikolay, Smolkova, Bozena, Staruchova, Marta, Stetina, Rudolf, Stopper, Helga, Surikova, Ekaterina I., Ulven, Stine M., Ursini, Cinzia Lucia, Valdiglesias, Vanessa, Valverde, Mahara, Vodicka, Pavel, Volkovova, Katarina, Wagner, Karl-Heinz, Živković, Lada, Dušinská, Maria, Collins, Andrew R., Bonassi, Stefano, "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" in Mutation Research - Reviews in Mutation Research, 787 (2021),
https://doi.org/10.1016/j.mrrev.2021.108371 . .
