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
摘要
体内彗星试验已被验证用于遗传毒性测试，并包括在ICH， ECHA和EFSA策略中。然而，OECD测试指南（TG） 489体内哺乳动物碱性彗星试验仅涵盖标准版本，检测DNA链断裂（SB）和碱不稳定位点（ALS），限制了机制的见解。内含甲酰胺嘧啶DNA糖基酶（Fpg），可检测氧化碱基；鉴定了52项使用酶揭示标准彗星测定法无法检测到的DNA病变的研究（Collins et al. 2020）。尽管使用频繁，但使用酶的研究中只有不到三分之一包括阳性对照，这将有助于标准化和经合组织TG 489的整合。本研究评估溴酸钾（KBrO3）作为一个潜在的阳性对照，为fpg修饰的彗星试验。按照OECD TG 489原则给Wistar大鼠灌胃两次不同剂量的KBrO3，观察肝、十二指肠、肾、脑和全血DNA损伤情况。标准版以甲磺酸乙酯（EMS）为阳性对照。加入Fpg消化提高了检测的敏感性和特异性，KBrO3诱导的DNA氧化损伤在3小时内检测到肾、肝和十二指肠，表明它可能是一个很好的阳性对照。
Evaluation of Potassium Bromate as a Positive Control in the In Vivo Fpg-Modified Comet Assay for the Detection of Oxidized 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 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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