INCORPORATION OF 5-FLUOROURACIL INTO HEPATOMA AND NORMAL TISSUE RNA AT PROTEIN DEPLETION IN THE RAT

Background and Objectives: 5-fluorouracil (5-FU) exerts its effects ma inly by its incorporation into RNA and inhibition of DNA synthesis. It s toxicity may therefore be estimated by measuring its incorporation i nto RNA. Protein malnutrition has been considered to increase the toxi city of 5-FU. Methods: Rats with a hepatoma implanted into the liver w ere fed on either a 25% or a 0% casein diet for 1 week. On the last da y, they were infused via the hepatic artery with a therapeutic dose of H-3-5-FU. Its incorporation into RNA was measured in hepatoma and sev eral normal tissues. Results: Protein deprivation increased the incorp oration of 5-FU into liver and intestinal RNA. Incorporation into hepa toma RNA did not increase significantly, but the ratio, liver/hepatoma RNA incorporation, remained unchanged. Conclusions: Protein deprivati on might increase the toxicity of 5-FU on liver and intestine. (C) 199 7 Wiley-Liss, Inc.