Radioautographic,ultrastructural and biochemical studies on the effect of fluorouracil on the RNA synthesis in the liver of rats

Summary The effects of fluorouracil and uracil on the ultrastructure and RNA synthesis in the liver of rats have been studied. High doses of uracil, contrary to fluorouracil, had no effects on nucleolar ultrastructure. Fluorouracil, even in low doses, depressed the RNA synthesis as studied after cytidine-³H administration. In the radioautographs the depression was especially seen to affect the cytoplasmic labelling. The biochemical analysis showed signs of a depression of ribosomal RNA synthesis and a block or delay in the maturation of ribosomal RNA. Repeated, high doses of uracil also depressed the RNA synthesis but there did not seem to be any delay in the maturation of ribosomal RNA. The results suggest that fluorouracil may affect the RNA metabolism in the nucleoli.The investigation was supported by grants from the Swedish Medical Research Council (Project K 67–12 X-623-03), the Swedish Cancer Society (Project 67:31) and the Medical Faculty of Uppsala.