Incorporation of 5-fluorouracil into rat liver tumor and normal tissues and the liver nucleotide profile after administration by the hepatic artery during portal venous branch ligation.
A therapeutic dose of labelled 5-fluorouracil (5-FU) was infused via the hepatic artery during 30 min with or without ligation of the left portal venous branch in Wistar rats with a secondary liver cancer in the left lateral lobe. After another 60 min, the incorporation of 5-FU into the acid soluble fraction (ASF), ribonucleic acid (RNA) and deoxyribonucleic acid (DNA), was determined in tumor, ligated and unligated liver lobes, small intestine, kidney, and bone marrow. The liver nucleotide profile was examined with isotachophoresis. Portal venous branch ligation (PVBL) caused the following changes, compared with the unligated control group: in the tumor, the incorporation of 5-FU into RNA and DNA decreased and the ratio RNA/acid-soluble fraction labelling decreased. The incorporation increased in intestinal and bone marrow RNA. It was unchanged in liver and kidney. The ratio of tumor to peripheral normal-tissue (small intestine, bone marrow, and kidney) labelling of RNA and DNA decreased. Liver nucleotides (F)UTP, (F)UDP-glucuronic acid, (F)UDP-N-acetylhexosamine, and NAD were lower in the ligated than in the unligated liver lobe. ATP and energy charge did not decrease significantly. In conclusion, PVBL in conjunction with hepatic arterial administration of 5-FU increased systemic drug exposure and possibly decreased hepatic tumor anabolism. It has not been examined how this interferes with the therapeutic effect.
Jakobsson
B
B
Department of Pathology, University of Lund, Sweden.
Roos
G
G
el Hag
I A
IA
Jönsson
P E
PE
Stenram
U
U
D000818:Animals; D004273:DNA, Neoplasm / Q000378:metabolism; D005472:Fluorouracil / Q000008:administration & dosage / Q000378:metabolism* / Q000493:pharmacokinetics; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008026:Ligation; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000098:blood supply / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D009711:Nucleotides; D011169:Portal Vein; D012334:RNA, Neoplasm / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D014018:Tissue Distribution
D004273:DNA, Neoplasm; D009711:Nucleotides; D012334:RNA, Neoplasm; D005472:Fluorouracil