E Saenz-Martinez, M Collia, A Rodriguez-Garraus, A G Gil, A López de Cerain, A Azqueta
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引用次数: 0
Abstract
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 methanesulfonate (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 hours indicating that it may be a good positive control.
期刊介绍：
Food and Chemical Toxicology (FCT), an internationally renowned journal, that publishes original research articles and reviews on toxic effects, in animals and humans, of natural or synthetic chemicals occurring in the human environment with particular emphasis on food, drugs, and chemicals, including agricultural and industrial safety, and consumer product safety. Areas such as safety evaluation of novel foods and ingredients, biotechnologically-derived products, and nanomaterials are included in the scope of the journal. FCT also encourages submission of papers on inter-relationships between nutrition and toxicology and on in vitro techniques, particularly those fostering the 3 Rs.
The principal aim of the journal is to publish high impact, scholarly work and to serve as a multidisciplinary forum for research in toxicology. Papers submitted will be judged on the basis of scientific originality and contribution to the field, quality and subject matter. Studies should address at least one of the following:
-Adverse physiological/biochemical, or pathological changes induced by specific defined substances
-New techniques for assessing potential toxicity, including molecular biology
-Mechanisms underlying toxic phenomena
-Toxicological examinations of specific chemicals or consumer products, both those showing adverse effects and those demonstrating safety, that meet current standards of scientific acceptability.
Authors must clearly and briefly identify what novel toxic effect (s) or toxic mechanism (s) of the chemical are being reported and what their significance is in the abstract. Furthermore, sufficient doses should be included in order to provide information on NOAEL/LOAEL values.
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