Relevant Aspects of Drug Genetic Toxicology

A. Durnev, A. Zhanataev
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引用次数: 2

Abstract

Genotoxic lesions are not only a cause of genetic pathologies and cancer, but also the most common and significant factor of the etiopathology of cardiovascular and neurodegenerative disorders, reproductive losses, infertility, and aging. This requires careful monitoring of the use of potential genotoxicants including medicinal products (MPs), which are a group of compounds intentionally and routinely used by humans. Genotoxicity assesment is highly essential in preclinical drug safety studies. The aim of the study was to analyse the current situation and reveal possible ways of addressing methodological and regulatory issues in genotoxicology to enable proper conduction of drug safety preclinical studies. The article summarises basic concepts of the modern genetic toxicology development and highlights the history of research aimed at identifying mutagenic, clastogenic, and aneugenic effects. The authors analyse regulatory aspects of genotoxicological studies of MPs and consider issues of improving the strategy for genotoxicity testing. The paper gives information about the genotoxicity tests approved for MPs, recommendations for interchangeability of tests in relation to particular study characteristics. The authors carried out a comparative analysis of the tests’ pros and cons with an emphasis that the study of each MP is a separate scientific task. They discuss interpretation of results and prediction of MP carcinogenic potential in genotoxicological studies. Recommendations are given for the optimisation of the MP genotoxicity assessment strategy, considering its partial integration into general toxicity studies. The article stresses the urgent need to develop registration methods for genotoxic events in germ cells, assesses the prospects of new tests, and reviews new trends in drug genotoxicology fundamental research.
药物遗传毒理学的相关方面
基因毒性病变不仅是遗传病理和癌症的原因,也是心血管和神经退行性疾病、生殖丧失、不孕和衰老的最常见和最重要的病因。这需要仔细监测潜在基因毒物的使用,包括医药产品(MPs),这是人类有意和常规使用的一组化合物。遗传毒性评估在临床前药物安全性研究中非常重要。本研究的目的是分析目前的情况,并揭示解决基因毒理学方法和监管问题的可能方法,以便正确开展药物安全性临床前研究。本文概述了现代遗传毒理学发展的基本概念,重点介绍了旨在确定致突变、致裂和非优生效应的研究历史。作者分析了MPs基因毒理学研究的监管方面,并考虑了改进遗传毒性测试策略的问题。本文提供了关于批准的MPs遗传毒性试验的信息,以及与特定研究特征相关的试验互换性的建议。作者对这些测试的优缺点进行了比较分析,强调对每一种MP的研究都是一项单独的科学任务。他们讨论了基因毒理学研究结果的解释和MP致癌潜力的预测。考虑到其部分整合到一般毒性研究中,提出了优化MP遗传毒性评估策略的建议。本文强调了开发生殖细胞遗传毒性事件登记方法的迫切需要,评估了新检测方法的前景,并综述了药物遗传毒理学基础研究的新趋势。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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