In vivo model of myelosuppression
Transplantation & Engraftment Kinetics in 5-FU Model
The 5-FU model is an excellent and well documented in vivo assay for monitoring myelosuppression (or protection) of various agents.
A common side effect following chemotherapeutic agent administration is myelosuppression leading to neutropenia. 5-fluorouracil (5-FU) is a DNA replication inhibitor that kills rapidly dividing cells (including neutrophil progenitors) while sparing more quiescent cells (such as resting stem cells). The single dose administration of 5-FU to mice at 150 mg/kg causes a significant and almost immediate (within 2 days) reduction in the white blood cell, neutrophil, and femoral bone marrow cellularity. Over the next 12 days, there is an initial gradual recovery of the bone marrow progenitors followed by recovery of neutrophil cell numbers. Compounds that augment the hematopoietic (e.g. G-CSF) system can be evaluated with this model.
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Applications of the In Vivo 5-FU Assay
- Detection of compounds that augment hematological recovery.
- Detection of compounds that “protect” or “spare” cells against chemotherapeutic agents.
- Evaluation of unexpected effects of novel compounds (antibodies, etc.) in “perturbed” situations.
- Assessment of the recovery of white blood cells, red blood cells and platelets in order to evaluate single lineage or multiple lineage effects.