Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases

The in vivo comet assay is validated for genotoxicity testing and included in ICH, ECHA, and EFSA strategies. However, OECD test guideline (TG) 489 In vivo Mammalian Alkaline Comet Assay covers only the standard version, detecting DNA strand breaks (SB) and alkali-labile sites (ALS), limiting mechan...

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Autores: Saenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ce, Collia, M. (Miguel)|||/items/c35af35f-5893-40de-a900-04439e68267f, Rodríguez-Garraus, A. (Adriana)|||/items/0a42fa69-ee9b-459d-8ddd-3dfa0ba4bbd4, Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53, Lopez-de-Cerain, A. (Adela)|||/items/8d95b72a-6816-4612-884b-5cf5c6c172f1, Azqueta, A. (Amaya)|||/items/f04b3c23-3ff4-41c8-b5e1-4d372fbc4893
Tipo de recurso: artículo
Fecha de publicación:2025
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:Dadun. Depósito Académico Digital de la Universidad de Navarra
Idioma:inglés
OAI Identifier:oai:dadun.unav.edu:10171/117148
Acceso en línea:https://hdl.handle.net/10171/117148
Access Level:acceso abierto
Palabra clave:Comet assay
DNA damage
In vivo
Enzyme
Potassium bromate
Positive control
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spelling Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised basesSaenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ceCollia, M. (Miguel)|||/items/c35af35f-5893-40de-a900-04439e68267fRodríguez-Garraus, A. (Adriana)|||/items/0a42fa69-ee9b-459d-8ddd-3dfa0ba4bbd4Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53Lopez-de-Cerain, A. (Adela)|||/items/8d95b72a-6816-4612-884b-5cf5c6c172f1Azqueta, A. (Amaya)|||/items/f04b3c23-3ff4-41c8-b5e1-4d372fbc4893Comet assayDNA damageIn vivoEnzymePotassium bromatePositive controlThe in vivo comet assay is validated for genotoxicity testing and included in ICH, ECHA, and EFSA strategies. However, OECD test guideline (TG) 489 In vivo Mammalian Alkaline Comet Assay covers only the standard version, detecting DNA strand breaks (SB) and alkali-labile sites (ALS), limiting mechanistic insights. Inclusion of the enzyme formamidopyrimidine DNA glycosylase (Fpg) allows detection of oxidised bases; 52 studies using enzymes to reveal DNA lesions undetectable with the standard comet assay were identified (Collins et al., 2020). Despite its frequent use, fewer than one-third of studies employing enzymes include positive controls, which would aid standardization and OECD TG 489 integration. The present study evaluates potassium bromate (KBrO3) as a potential positive control for the Fpg-modified comet assay. Wistar rats were dosed twice by oral gavage with different doses of KBrO3 following OECD TG 489 principles, with DNA damage assessed in liver, duodenum, kidney, brain, and whole blood. Ethyl meth- anesulfonate (EMS) was used as a positive control for the standard version. The inclusion of Fpg digestion enhances assay sensitivity and specificity, and DNA oxidation damage induced by KBrO3 is detected in kidney, liver, and duodenum within 3 h, indicating that it may be a good positive control.Elsevier Ltd.Dadun. Depósito Académico Digital Universidad de Navarra20252025-01-0120252025-01-01journal articlehttp://purl.org/coar/resource_type/c_6501info:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/10171/117148reponame:Dadun. Depósito Académico Digital de la Universidad de Navarrainstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglésengopen accesshttp://purl.org/coar/access_right/c_abf2info:eu-repo/semantics/openAccessoai:dadun.unav.edu:10171/1171482026-06-21T12:47:57Z
dc.title.none.fl_str_mv Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
title Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
spellingShingle Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
Saenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ce
Comet assay
DNA damage
In vivo
Enzyme
Potassium bromate
Positive control
title_short Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
title_full Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
title_fullStr Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
title_full_unstemmed Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
title_sort Evaluation of potassium bromate as a positive control in the in vivo Fpg-modified comet assay for the detection of oxidised bases
dc.creator.none.fl_str_mv Saenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ce
Collia, M. (Miguel)|||/items/c35af35f-5893-40de-a900-04439e68267f
Rodríguez-Garraus, A. (Adriana)|||/items/0a42fa69-ee9b-459d-8ddd-3dfa0ba4bbd4
Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53
Lopez-de-Cerain, A. (Adela)|||/items/8d95b72a-6816-4612-884b-5cf5c6c172f1
Azqueta, A. (Amaya)|||/items/f04b3c23-3ff4-41c8-b5e1-4d372fbc4893
author Saenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ce
author_facet Saenz-Martínez, E. (E.)|||/items/b8f8f696-c821-45c5-b959-74f1128e07ce
Collia, M. (Miguel)|||/items/c35af35f-5893-40de-a900-04439e68267f
Rodríguez-Garraus, A. (Adriana)|||/items/0a42fa69-ee9b-459d-8ddd-3dfa0ba4bbd4
Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53
Lopez-de-Cerain, A. (Adela)|||/items/8d95b72a-6816-4612-884b-5cf5c6c172f1
Azqueta, A. (Amaya)|||/items/f04b3c23-3ff4-41c8-b5e1-4d372fbc4893
author_role author
author2 Collia, M. (Miguel)|||/items/c35af35f-5893-40de-a900-04439e68267f
Rodríguez-Garraus, A. (Adriana)|||/items/0a42fa69-ee9b-459d-8ddd-3dfa0ba4bbd4
Gil-Royo, A.G. (Ana Gloria)|||/items/f54744d1-e54a-42e1-b5d0-cbabefd3fc53
Lopez-de-Cerain, A. (Adela)|||/items/8d95b72a-6816-4612-884b-5cf5c6c172f1
Azqueta, A. (Amaya)|||/items/f04b3c23-3ff4-41c8-b5e1-4d372fbc4893
author2_role author
author
author
author
author
dc.contributor.none.fl_str_mv Dadun. Depósito Académico Digital Universidad de Navarra
dc.subject.none.fl_str_mv Comet assay
DNA damage
In vivo
Enzyme
Potassium bromate
Positive control
topic Comet assay
DNA damage
In vivo
Enzyme
Potassium bromate
Positive control
description The in vivo comet assay is validated for genotoxicity testing and included in ICH, ECHA, and EFSA strategies. However, OECD test guideline (TG) 489 In vivo Mammalian Alkaline Comet Assay covers only the standard version, detecting DNA strand breaks (SB) and alkali-labile sites (ALS), limiting mechanistic insights. Inclusion of the enzyme formamidopyrimidine DNA glycosylase (Fpg) allows detection of oxidised bases; 52 studies using enzymes to reveal DNA lesions undetectable with the standard comet assay were identified (Collins et al., 2020). Despite its frequent use, fewer than one-third of studies employing enzymes include positive controls, which would aid standardization and OECD TG 489 integration. The present study evaluates potassium bromate (KBrO3) as a potential positive control for the Fpg-modified comet assay. Wistar rats were dosed twice by oral gavage with different doses of KBrO3 following OECD TG 489 principles, with DNA damage assessed in liver, duodenum, kidney, brain, and whole blood. Ethyl meth- anesulfonate (EMS) was used as a positive control for the standard version. The inclusion of Fpg digestion enhances assay sensitivity and specificity, and DNA oxidation damage induced by KBrO3 is detected in kidney, liver, and duodenum within 3 h, indicating that it may be a good positive control.
publishDate 2025
dc.date.none.fl_str_mv 2025
2025-01-01
2025
2025-01-01
dc.type.none.fl_str_mv journal article
http://purl.org/coar/resource_type/c_6501
dc.type.openaire.fl_str_mv info:eu-repo/semantics/article
format article
dc.identifier.none.fl_str_mv https://hdl.handle.net/10171/117148
url https://hdl.handle.net/10171/117148
dc.language.none.fl_str_mv Inglés
eng
language_invalid_str_mv Inglés
language eng
dc.rights.none.fl_str_mv open access
http://purl.org/coar/access_right/c_abf2
dc.rights.openaire.fl_str_mv info:eu-repo/semantics/openAccess
rights_invalid_str_mv open access
http://purl.org/coar/access_right/c_abf2
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.publisher.none.fl_str_mv Elsevier Ltd.
publisher.none.fl_str_mv Elsevier Ltd.
dc.source.none.fl_str_mv reponame:Dadun. Depósito Académico Digital de la Universidad de Navarra
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str Dadun. Depósito Académico Digital de la Universidad de Navarra
collection Dadun. Depósito Académico Digital de la Universidad de Navarra
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,812455

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