The role of diet on 5-fluorouracil toxicity

In three experiments performed at two month intervals, rats eating a nutritionally adequate defined-formula diet (DFD) exhibit a remarkable similarity in the response to 5-FU as measured by survival time, leukopenia and weight loss. Conversely, the corresponding control groups eating the standard Purina rat food show a different degree of tolerance to 5-FU, which varies from a level similar to that of the DFD groups to twice that value. It is suggested that certain protective factors against 5-FU toxicity present in natural food are absent in formula diets produced on the basis of standard requirements for normal growth and nutrition. The present studies indicate that such protective factors are neither vegetable fibers nor arachidonic acid. The importance of food intake in experimental toxicology and clinical pharmacology is emphasized.