The incorporation of 5-fluorouracil into rat liver tumor and normal tissues after administration by the hepatic artery during temporary portal vein clamping.
A therapeutic dose of labelled 5-fluorouracil (5-FU) was infused via the hepatic artery during 30 min with or without a simultaneous temporary clamping of the portal vein in a model of secondary liver cancer in Wistar rats. After another 60 min, the incorporation of 5-FU into the acid soluble fraction, RNA and DNA was determined in tumor, liver, small intestine, kidney, and bone marrow. The liver and intestinal nucleotide profiles were examined with isotachophoresis. Temporary portal vein clamping caused the following changes, as compared with the control group with intraarterial infusion only: in the liver, the incorporation of 5-FU into the acid soluble fraction increased without a concomitant increase into the RNA or of the level of (F)UTP. Liver ATP decreased. In the tumor, the ratio of RNA to acid soluble fraction labelling decreased. There was a generally decreased ratio of tumor to peripheral normal tissue (small intestine and kidney) labelling. In conclusion, portal vein clamping in conjunction with hepatic arterial administration of 5-FU led to a decreased anabolism of 5-FU in the liver and tumor, and increased systemic drug exposure. It is not known how this interferes with the therapeutic effect.
Department of Pathology, University of Lund, Sweden.
I A
IA
el Hag
B
B
Jakobsson
P E
PE
Jönsson
U
U
Stenram
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003250:Constriction; D004247:DNA / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism*; D006499:Hepatic Artery; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary; D008297:Male; D011169:Portal Vein; D012313:RNA / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D012313:RNA; D000255:Adenosine Triphosphate; D004247:DNA; D005472:Fluorouracil