Environmental Stress & Cancer Group, National Institute of Environmental Health Sciences, Mail Drop D2-03, PO Box 12233, 111 TW Alexander Drive, Research Triangle Park, NC 27709, USA.
Pharmacogenomics. 2010 Apr;11(4):573-85. doi: 10.2217/pgs.10.37.
Adverse drug reactions (ADRs) are an important clinical issue and a serious public health risk. Understanding the underlying mechanisms is critical for clinical diagnosis and management of different ADRs. Toxicogenomics can reveal impacts on biological pathways and processes that had not previously been considered to be involved in a drug response. Mechanistic hypotheses can be generated that can then be experimentally tested using the full arsenal of pharmacology, toxicology, molecular biology and genetics. Recent transcriptomic studies on drug-induced toxicity, which have provided valuable mechanistic insights into various ADRs, have been reviewed with a focus on nephrotoxicity and hepatotoxicity. Related issues have been discussed, including extrapolation of mechanistic findings from experimental model systems to humans using blood as a surrogate tissue for organ damage and comparative systems biology approaches.
药物不良反应(ADRs)是一个重要的临床问题,也是一个严重的公共卫生风险。了解潜在的机制对于临床诊断和管理不同的 ADR 至关重要。毒理基因组学可以揭示对生物途径和过程的影响,这些途径和过程以前被认为与药物反应无关。可以生成机制假设,然后使用药理学、毒理学、分子生物学和遗传学的全套方法进行实验测试。最近关于药物引起的毒性的转录组学研究为各种 ADR 提供了有价值的机制见解,本文对此进行了综述,重点讨论了肾毒性和肝毒性。还讨论了相关问题,包括使用血液作为器官损伤的替代组织,将实验模型系统中的机制发现外推到人类,以及比较系统生物学方法。