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使用波动Ames试验研究2,6-二甲基吡啶-N-氧化物的抗诱变作用。

Antimutagenic effects of 2,6-Dimethylpyridine-N-oxide using fluctuation ames test.

作者信息

Vasetska Olesia, Bubalo Volodymyr, Usenko Tetyana, Zhminko Petro, Prodanchuk Mykola

机构信息

L.I. Medved's Research Center of Preventive Toxicology, Food and Chemical Safety, Ministry of Health Ukraine, SE, Laboratory of Experimental Toxicology and Mutagenesis, Kyiv, Ukraine.

出版信息

Toxicol Rep. 2025 Mar 5;14:101989. doi: 10.1016/j.toxrep.2025.101989. eCollection 2025 Jun.

Abstract

The mutagenic potential of chemical agents is a significant concern in the field of genetic toxicology. The 2,6-Dimethylpyridine-N-oxide is believed to have antimutagenic properties, which could be beneficial for applications in pharmaceutical and environmental sciences. This study aims to evaluate the antigenotoxic potential of 2,6-Dimethylpyridine-N-oxide using the fluctuation Ames test, a reliable method for detecting mutagenic effect. Specifically, the Ames assay was conducted with preincubation in a suspension of reversion Salmonella bacteria. The experimental approach utilized tester strains - TA98, which are characterized by frameshift mutations in the hisD3052 gene, and another strain TA100 featuring base-pair substitution mutations in the hisG46 gene to assess the genotoxic potential of the test compounds. The aim was to evaluate the antigenotoxic potential, these strains were concurrently exposed to positive mutagens: 4-Nitroquinoline-N-oxide (4-NQO) for the strain TA100 and 2-Nitrofluorene (2-NF) for TA98, without the presence of rat liver S9 microsomal fractions. Additionally, 2-Aminoanthracene (2-AA) was used for both strains with S9 activation alongside 2,6-Dimethylpyridine-N-oxide with the same dose level as positive controls by volume. The results indicate that 2,6-Dimethylpyridine-N-oxide exhibits significant antimutagenic effect, as shown by a notable reduction in mutation rates detected by the fluctuation Ames test. These findings support further investigation into the role of 2,6-Dimethylpyridine-N-oxide in preventing mutagenesis and its potential utility in drug development and environmental protection. This research provides essential insights into anti-mutagenesis and highlights the potential of 2,6-Dimethylpyridine-N-oxide in mitigating genotoxic risks.

摘要

化学试剂的诱变潜力是遗传毒理学领域的一个重大关注点。2,6-二甲基吡啶-N-氧化物被认为具有抗诱变特性,这可能对制药和环境科学领域的应用有益。本研究旨在使用波动Ames试验评估2,6-二甲基吡啶-N-氧化物的抗遗传毒性潜力,波动Ames试验是一种检测诱变效应的可靠方法。具体而言,Ames试验在回复型沙门氏菌的悬浮液中进行预孵育。实验方法使用了测试菌株——TA98,其特征是hisD3052基因发生移码突变,以及另一个菌株TA100,其在hisG46基因中具有碱基对取代突变,以评估受试化合物的遗传毒性潜力。目的是评估抗遗传毒性潜力,这些菌株同时暴露于阳性诱变剂:TA100菌株使用4-硝基喹啉-N-氧化物(4-NQO),TA98菌株使用2-硝基芴(2-NF),且不存在大鼠肝S9微粒体组分。此外,2-氨基蒽(2-AA)在有S9激活的情况下用于这两种菌株,同时2,6-二甲基吡啶-N-氧化物与阳性对照按体积计具有相同剂量水平。结果表明,2,6-二甲基吡啶-N-氧化物表现出显著的抗诱变作用,波动Ames试验检测到的突变率显著降低即表明了这一点。这些发现支持进一步研究2,6-二甲基吡啶-N-氧化物在预防诱变中的作用及其在药物开发和环境保护中的潜在用途。本研究为抗诱变提供了重要见解,并突出了2,6-二甲基吡啶-N-氧化物在减轻遗传毒性风险方面的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/585b/11950738/8199e59790e2/gr1.jpg

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