Effects of protein-calorie malnutrition and refeeding on fluorouracil toxicity
R. L. Gamelli and R. S. Foster Jr
Mice were used to study the effects of protein-calorie malnutrition and its
reversal on granulocyte-macrophage production and fluorouracil's toxic
effect on bone marrow. An in vitro quantitative clonal culture technique
for bone marrow granulocyte-macrophage progenitor cells (GM-CFC) was used.
Animals on a protein-free but otherwise complete diet for ten days had a
significant contraction in total marrow cellularity and GM-CFC numbers
paralleling the animal's weight loss. The acute toxic effect of
fluorouracil on bone marrow was not increased in protein-deprived animals.
On refeeding, there was a biphasic response in the degree of toxic effect
on marrow. Animals refed for one day had significantly increased
fluorouracil-related marrow abnormalities. However, animals refed for four
days, when marrows were repleted, were partially protected from the drug's
cytotoxic effects. The increased sensitivity in mice refed for one day was
related to more GM-CFC in active DNA synthesis.
