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.
Roos
G
G
Department of Pathology, Lund University, Sweden.
Stenram
U
U
D000230:Adenocarcinoma / Q000139:chemically induced / Q000378:metabolism / Q000556:secondary*; D000818:Animals; D001853:Bone Marrow / Q000187:drug effects / Q000378:metabolism; D003110:Colonic Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004127:Dimethylhydrazines; D005472:Fluorouracil / Q000378:metabolism*; D007370:Interferon Type I / Q000494:pharmacology*; D007421:Intestine, Small / Q000187:drug effects / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary*; D008297:Male; D011070:Poly I-C / Q000494:pharmacology*; D012313:RNA / Q000096:biosynthesis* / Q000187:drug effects; D012334:RNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012265:Ribonucleotides / Q000378:metabolism
D004127:Dimethylhydrazines; D007370:Interferon Type I; D012334:RNA, Neoplasm; D012265:Ribonucleotides; D012313:RNA; D004247:DNA; D011070:Poly I-C; D005472:Fluorouracil