The effect of protein depletion on bone marrow myeloid cell repopulation

We studied the effect of protein depletion on bone marrow recovery after injection of the cytotoxic drug, 5-fluorouracil (5-FU), by using an in vitro quantitative clonal culture technique for femoral marrow granulocyte/macrophage progenitor cells (GM-CFC). Mice were maintained for 7 days on either a regular diet or on a protein-free but isocaloric and otherwise complete diet. Groups of animals were assayed 1–5 and 7 days after 40 mg/kg ip 5-FU. Both regular-diet animals and animals on the protein-free diet had similar GM-CFC toxicity 1 day after 5-FU injection. However, 5 days after 5-FU, protein-depleted animals were significantly different from regular diet animals in the extent of repopulation of the GM-CFC (confidence 95%). Regular diet animals demonstrated a rebound overshoot of the progenitor cells which was not found in protein-depleted animals. The extent of recovery of the GM-CFC at 7 days after 5-FU for the protein-depleted animals still did not equal that of the regular diet animals (90% confidence). Quadratic regression analysis of the recovery curves for both regular diet and protein-free diet animals for Days 1–7 following 5-FU were significantly different (P < 0.01). We conclude that while protein depletion does not alter the acute bone marrow toxicity of 5-FU, protein-depleted animals had an impaired rate and extent of repopulation of the myeloid progenitor cells. These findings may form the basis for a clinical policy of dietary repletion in selected malnourished cancer patients prior to chemotherapeutic treatment.