Boorman Gary A, Anderson Steven P, Casey Warren M, Brown Roger H, Crosby Lynn M, Gottschalk K, Easton Marilyn, Ni Hong, Morgan Kevin T
Laboratory for Experimental Pathology, Environmental Toxicology Program, NIEHS, Research Triangle Park, NC 27709, USA.
Toxicol Pathol. 2002 Jan-Feb;30(1):15-27. doi: 10.1080/01926230252824671.
The field of toxicogenomics, which currently focuses on the application of large-scale differential gene expression (DGE) data to toxicology, is starting to influence drug discovery and development in the pharmaceutical industry. Toxicological pathologists, who play key roles in the development of therapeutic agents, have much to contribute to DGE studies, especially in the experimental design and interpretation phases. The intelligent application of DGE to drug discovery can reveal the potential for both desired (therapeutic) and undesired (toxic) responses. The pathologist's understanding of anatomic, physiologic, biochemical, immune, and other underlying factors that drive mechanisms of tissue responses to noxious agents turns a bewildering array of gene expression data into focused research programs. The latter process is critical for the successful application of DGE to toxicology. Pattern recognition is a useful first step, but mechanistically based DGE interpretation is where the long-term future of these new technologies lies. Pathologists trained to carry out such interpretations will become important members of the research teams needed to successfully apply these technologies to drug discovery and safety assessment. As a pathologist using DGE, you will need to learn to read DGE data in the same way you learned to read glass slides, patiently and with a desire to learn and, later, to teach. In return, you will gain a greater depth of understanding of cell and tissue function, both in health and disease.
毒理基因组学领域目前专注于将大规模差异基因表达（DGE）数据应用于毒理学，正开始影响制药行业的药物发现和开发。毒理病理学家在治疗药物的开发中发挥着关键作用，对DGE研究有很大贡献，尤其是在实验设计和解释阶段。将DGE智能应用于药物发现可以揭示预期（治疗）和非预期（毒性）反应的可能性。病理学家对驱动组织对有害剂反应机制的解剖学、生理学、生物化学、免疫学和其他潜在因素的理解，将一系列令人困惑的基因表达数据转化为重点研究项目。后一过程对于DGE在毒理学中的成功应用至关重要。模式识别是有用的第一步，但基于机制的DGE解释才是这些新技术的长期未来所在。经过培训能够进行此类解释的病理学家将成为成功将这些技术应用于药物发现和安全评估所需研究团队的重要成员。作为一名使用DGE的病理学家，你需要学会像学习阅读玻片一样阅读DGE数据，耐心且有求知欲，之后还要传授知识。作为回报，你将对健康和疾病状态下的细胞和组织功能有更深入的理解。
