The Center for Alternatives to Animal Testing is an academic center affiliated with the Division of Toxicological Sciences in the Department of Environmental Health Sciences of the Johns Hopkins University Bloomberg School of Public Health.

 

Johns Hopkins School of Public Health

Research Grants 1999-2000

Comparison of Semi-Solid and Suspension Assays for the Evaluation of Thrombocytopenia-Inducing Agents

Donna A. Volpe, PhD
Food and Drug Administration, Laurel, Maryland

In the treatment of cancer with drugs, a frequent harmful effect is the decrease in the number of blood cells. One cell type that can be reduced is the platelet, which is involved in blood clot formation. A severe decrease in the number of circulating platelets, called thrombocytopenia, can result in life-threatening hemorrhage, or uncontrolled bleeding. As strategies to alleviate thrombocytopenia improve, it would be beneficial to understand a new drug's potential to reduce platelet counts in patients. Megakaryocytes in the marrow give rise to functional platelets through the processes of proliferation and maturation. Hematopoietic clonal assays are utilized during drug development as a method of predicting bone marrow toxicity. Megakaryocyte progenitors are routinely cultured in semi-solid assays that are tedious, time consuming and subjective. A more effective alternative is a liquid suspension assay that evaluates drug effects by measuring the megakaryocyte population by flow cytometry. The specific aims of the study are to:

These in vitro methods use human cells to predict a frequent clinical dose-limiting toxicity during cancer therapy. Such a refinement can lead to the reduction of animal studies in preclinical drug development and a better predictive model eliminating the need for interspecies extrapolations.