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秀丽隐杆线虫作为一种强大的替代模式生物,可促进遗传毒理学和生物医学研究。

Caenorhabditis elegans as a powerful alternative model organism to promote research in genetic toxicology and biomedicine.

作者信息

Honnen Sebastian

机构信息

Medical Faculty, Institute of Toxicology, Heinrich Heine University Düsseldorf, 40225, Düsseldorf, Germany.

出版信息

Arch Toxicol. 2017 May;91(5):2029-2044. doi: 10.1007/s00204-017-1944-7. Epub 2017 Mar 15.

Abstract

In view of increased life expectancy the risk for disturbed integrity of genetic information increases. This inevitably holds the implication for higher incidence of age-related diseases leading to considerable cost increase in health care systems. To develop preventive strategies it is crucial to evaluate external and internal noxae as possible threats to our DNA. Especially the interplay of DNA damage response (DDR) and DNA repair (DR) mechanisms needs further deciphering. Moreover, there is a distinct need for alternative in vivo test systems for basic research and also risk assessment in toxicology. Especially the evaluation of combinational toxicity of environmentally present genotoxins and adverse effects of clinically used DNA damaging anticancer drugs is a major challenge for modern toxicology. This review focuses on the applicability of Caenorhabditis elegans as a model organism to unravel and tackle scientific questions related to the biological consequences of genotoxin exposure and highlights methods for studying DDR and DR. In this regard large-scale in vivo screens of mixtures of chemicals and extensive parallel sequencing are highlighted as unique advantages of C. elegans. In addition, concise information regarding evolutionary conserved molecular mechanisms of the DDR and DR as well as currently available data obtained from the use of prototypical genotoxins and preferential read-outs of genotoxin testing are discussed. The use of established protocols, which are already available in the community, is encouraged to facilitate and further improve the implementation of C. elegans as a powerful genetic model system in genetic toxicology and biomedicine.

摘要

鉴于预期寿命的延长,遗传信息完整性受到干扰的风险增加。这不可避免地意味着与年龄相关疾病的发病率更高,导致医疗保健系统的成本大幅增加。为了制定预防策略,评估外部和内部有害物质作为对我们DNA的潜在威胁至关重要。特别是DNA损伤反应(DDR)和DNA修复(DR)机制之间的相互作用需要进一步解读。此外,迫切需要用于基础研究以及毒理学风险评估的替代体内测试系统。尤其是评估环境中存在的基因毒素的联合毒性以及临床使用的DNA损伤抗癌药物的不良反应,是现代毒理学面临的一项重大挑战。本综述重点关注秀丽隐杆线虫作为模式生物在揭示和解决与基因毒素暴露的生物学后果相关的科学问题方面的适用性,并强调研究DDR和DR的方法。在这方面,大规模体内化学混合物筛选和广泛的平行测序被突出为秀丽隐杆线虫的独特优势。此外,还讨论了关于DDR和DR的进化保守分子机制的简明信息,以及目前从使用典型基因毒素获得的数据和基因毒素测试的优先读数。鼓励使用社区中已经可用的既定方案,以促进并进一步改善秀丽隐杆线虫作为遗传毒理学和生物医学中强大的遗传模型系统的应用。

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