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Toxicogenomics - What added Value Do These Approaches Provide for Carcinogen Risk Assessment?

机译：毒理基因组学-这些方法为致癌物风险评估提供了哪些附加价值？

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It is still a major challenge to protect humans at workplaces and in the environment. To cope with this task, it is a prerequisite to obtain detailed information on the extent of chemical perturbations of biological pathways, in particular, adaptive vs. adverse effects and the dose-response relationships. This knowledge serves as the basis for the classification of non-carcinogens and carcinogens and for further distinguishing carcinogens in genotoxic (DNA damaging) or non-genotoxic compounds. Basing on quantitative dose-response relationships, points of departures can be derived for chemical risk assessment. In recent years, new methods have shown their capability to support the established rodent models of carcinogenicity testing. In vitro high throughput screening assays assess more comprehensively cell response. In addition, omics technologies were applied to study the mode of action of chemicals whereby the term "toxicogenomics" comprises various technologies such as transcriptomics, epigenomics, or metabolomics. This review aims to summarize the current state of toxicogenomic approaches in risk science and to compare them with established ones. For example, measurement of global transcriptional changes generates meaningful information for toxicological risk assessment such as accurate classification of genotoxicon-genotoxic carcinogens. Alteration in mRNA expression offers previously unknown insights in the mode of action and enables the definition of key events. Based on these, benchmark doses can be calculated for the transition from an adaptive to an adverse state. In short, this review assesses the potential and challenges of transcriptomics and addresses the impact of other omics technologies on risk assessment in terms of hazard identification and dose-response assessment.
机译：在工作场所和环境中保护人类仍然是一项重大挑战。为了完成这项任务，必须获得有关生物学途径化学扰动程度的详细信息，特别是适应性与不良作用以及剂量反应关系的详细信息。这些知识为非致癌物和致癌物的分类以及进一步区分遗传毒性（DNA破坏）或非遗传毒性化合物中的致癌物奠定了基础。基于定量的剂量反应关系，可以得出出发点以进行化学风险评估。近年来，新方法已经显示出它们能够支持已建立的致癌性测试啮齿动物模型的能力。体外高通量筛选分析可更全面地评估细胞反应。另外，组学技术被用于研究化学物质的作用方式，其中术语“毒理基因组学”包括各种技术，例如转录组学，表观基因组学或代谢组学。这篇综述旨在总结风险科学中毒物基因组学方法的现状，并将其与已建立的方法进行比较。例如，对全球转录变化的测量可为毒理学风险评估提供有意义的信息，例如遗传毒性/非遗传毒性致癌物的准确分类。 mRNA表达的改变提供了以前未知的作用方式见解，并能够定义关键事件。基于这些，可以计算出从适应状态到不良状态的基准剂量。简而言之，本综述评估了转录组学的潜力和挑战，并从危害识别和剂量反应评估的角度探讨了其他组学技术对风险评估的影响。

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