Incorporation of 5-fluorouracil into RNA of normal tissues and an adenocarcinoma in protein-deprived rats

Abstract

One of the main cytotoxic effects of 5-FU is its incorporation into RNA. In rats, protein deprivation increases the incorporation of labelled precursors into liver RNA. We examined the effect of protein deprivation on the incorporation of a therapeutic dose of 5-FU into the liver, small intestine, kidney and bone marrow and into an adenocarcinoma transplanted to the liver in the rat. The rats were fed either on a 25% or a 0% casein diet for one week. Some rats from both groups were given amino acids or glucose parenterally. Therapeutic 5-[3H]-FU was given in a 2 h infusion by the hepatic artery and the rats were sacrificed one h later. Incorporation into liver and intestinal RNA increased significantly with protein deprivation. The increase was largely eliminated by parenteral feeding of amino acids. No differences were found in incorporation into tumor and bone marrow RNA in protein deprivation. Incorporation into the acid soluble fraction and DNA is also reported.