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遗传毒性测试:未来十年的进展与展望

Genotoxicity testing: progress and prospects for the next decade.

作者信息

Turkez Hasan, Arslan Mehmet E, Ozdemir Ozlem

机构信息

a Faculty of Science, Department of Molecular Biology and Genetics , Erzurum Technical University , Erzurum , Turkey.

b Department of Pharmacy , University 'G. d'Annunzio' , Chieti , Italy.

出版信息

Expert Opin Drug Metab Toxicol. 2017 Oct;13(10):1089-1098. doi: 10.1080/17425255.2017.1375097. Epub 2017 Sep 10.

DOI:10.1080/17425255.2017.1375097
PMID:28889778
Abstract

Genotoxicity and mutagenicity analyses have a significant role in the identification of hazard effects of therapeutic drugs, cosmetics, agrochemicals, industrial compounds, food additives, natural toxins and nanomaterials for regulatory purposes. To evaluate mutagenicity or genotoxicity, different in vitro and in vivo methodologies exert various genotoxicological endpoints such as point mutations, changes in number and structure of chromosomes. Areas covered: This review covered the basics of genotoxicity and in vitro/in vivo methods for determining of genetic damages. The limitations that have arisen as a result of the common use of these methods were also discussed. Finally, the perspectives of further prospects on the use of genotoxicity testing and genotoxic mode of action were emphasized. Expert opinion: The solution of actual and practical problems of genetic toxicology is inarguably based on the understanding of DNA damage mechanisms at molecular, subcellular, cellular, organ, system and organism levels. Current strategies to investigate human health risks should be modified to increase their performance for more reliable results and also new techniques such as toxicogenomics, epigenomics and single cell approaches must be integrated into genetic safety evolutions. The explored new biomarkers by the omic techniques will provide forceful genotoxicity assessment to reduce the cancer risk.

摘要

遗传毒性和致突变性分析在鉴定治疗药物、化妆品、农用化学品、工业化合物、食品添加剂、天然毒素和纳米材料的危害效应以用于监管目的方面具有重要作用。为了评估致突变性或遗传毒性,不同的体外和体内方法会产生各种遗传毒理学终点,如点突变、染色体数量和结构的变化。涵盖领域:本综述涵盖了遗传毒性的基础知识以及用于确定遗传损伤的体外/体内方法。还讨论了由于这些方法的普遍使用而产生的局限性。最后,强调了遗传毒性测试和遗传毒性作用模式的进一步应用前景。专家观点:遗传毒理学实际和现实问题的解决无疑基于对分子、亚细胞、细胞、器官、系统和生物体水平上DNA损伤机制的理解。应改进当前调查人类健康风险的策略,以提高其性能以获得更可靠的结果,并且必须将毒理基因组学、表观基因组学和单细胞方法等新技术整合到遗传安全性评估中。通过组学技术探索的新生物标志物将为降低癌症风险提供有力的遗传毒性评估。

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