Interferon and the incorporation of 5-fluorouracil into RNA of normal tissues and a secondary liver carcinoma in rat.

The cytotoxicity of 5-fluorouracil (5-FU) has been related to its incorporation into RNA and blocking of DNA synthesis. Interferon may enhance the therapeutic efficacy of 5-FU in colorectal cancer. In a model of secondary liver cancer in the rat, the incorporation of 5-FU into the acid-soluble fraction (ASF), RNA and DNA of several normal tissues and the tumor was determined. The liver nucleotide profile and NADPH-cytochrome c reductase activity was examined. A therapeutic dose of 5-FU was given for 2 h via the hepatic artery and the rats were killed 1 h later. Half of them were pretreated with the interferon inducer polyinosinic-polycytidylic acid (poly(I)-poly(C) and interferon. Pretreatment increased the nucleotide (NT)/DNA and RNA/DNA ratios, decreased the cellularity and left the specific RNA labelling unchanged in the bone marrow. In the liver the pretreatment decreased the NT/DNA and RNA/DNA ratios, (F)UTP, and the NADPH-cytochrome c reductase activity. The 5-FU incorporation into liver DNA decreased. No changes were found in the tumor. The pretreated rats decreased in body weight. A decreased RNA synthesis in the liver might indicate a decreased 5-FU metabolism, explaining the increased 5-FU AUC in the clinic at interferon treatment.