Reagan William J, Irizarry-Rovira Armando, Poitout-Belissent Florence, Bolliger Anne Provencher, Ramaiah Shashi K, Travlos Greg, Walker Dana, Bounous Denise, Walter Gail
Pfizer, Inc., Groton, Connecticut, USA.
Toxicol Pathol. 2011 Feb;39(2):435-48. doi: 10.1177/0192623310396907. Epub 2011 Feb 7.
This manuscript is intended to provide a best practice approach to accurately and consistently assess toxicant-induced bone marrow effects of test articles. In nonclinical toxicity studies, complete blood count data in conjunction with the histological examination of the bone marrow are recommended as the foundation for assessing the effect of test articles on the hematopoietic system. This approach alone can be used successfully in many studies. However, in some situations it may be necessary to further characterize effects on the different hematopoietic lineages, either by cytological or flow cytometric evaluation of the bone marrow. Both modalities can be used successfully, and which one is selected will depend on the expertise, preference of the facility, and the nature of the change in the bone marrow. Other specialized techniques such as clonogenic assays or electron microscopy are used rarely to further characterize hematotoxicity. The indications and techniques to successfully employ histological, cytological, or flow cytometric evaluation as well as clonogenic assays and electron microscopy are reviewed.
本手稿旨在提供一种最佳实践方法，以准确且一致地评估受试物对骨髓的毒性作用。在非临床毒性研究中，建议将全血细胞计数数据与骨髓组织学检查相结合，作为评估受试物对造血系统影响的基础。仅这种方法就可在许多研究中成功应用。然而，在某些情况下，可能需要通过骨髓细胞学或流式细胞术评估来进一步明确对不同造血谱系的影响。这两种方法都可成功使用，选择哪种方法将取决于专业知识、机构的偏好以及骨髓变化的性质。其他专门技术，如克隆形成试验或电子显微镜检查，很少用于进一步明确血液毒性。本文综述了成功应用组织学、细胞学或流式细胞术评估以及克隆形成试验和电子显微镜检查的指征和技术。
