Using a Murine Erythroleukemia Cell Line to Evaluate the Potential Toxicity of Test Compounds
Knobloch, Hillary N.
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The potential toxicologic effects of test compounds on hematopoiesis are examined in preclinical animal studies by evaluating bone marrow and peripheral blood hematology. If effects on bone marrow are observed, these can be further characterized using in vitro cell culture systems. Murine erythroleukemia cells (MELC) are a well-characterized cell line that can be induced to differentiate into erythroid progenitors, one of the cell lineages present in bone marrow. The effects on MELC differentiation, cell cycle, and Annexin V (AnnV) and propidium iodide (PI) staining were examined with test compounds that had demonstrated effects on bone marrow in animals. DRUG 1, DRUG 2, and chloramphenicol caused dose-dependent increases in double-positive Ann V and PI MELC, indicating that the cells were in late apoptosis or necrosis. HMBA-induced MELC were more sensitive to the compound-related increases in Ann V / PI positive cells. The test compounds did not alter differentiation or cell cycle in HMBA-induced cells. MELC may be prove to be a useful cell line for the study of test compounds that demonstrate bone marrow toxicity in preclinical animal studies.