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
Descripción
Sumario: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.

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