Partial hepatectomy alters sensitivity of rat hepatocytes to 5-fluorouracil.
The sensitivity to 5-fluorouracil (5-FU) and the metabolism of 5-FU in the regenerating rat liver were investigated in vitro. Determination of cell viability using the succinate dehydrogenase inhibition test showed that the hepatocytes of the partially hepatectomized liver were more sensitive to 5-FU, compared to findings in the case of normal liver. The activities of 5-FU phosphorylation of the 3 pathways were higher in the regenerating than in the intact liver and the peak increase was seen 36 h after partial hepatectomy. The activity of 5-FU degradation decreased to about 30% at 36 h and then gradually increased reaching the normal range at 72 h after partial hepatectomy. These results suggest that the metabolic changes of 5-FU may be one of the causes for increased 5-FU susceptibility in the regenerating liver.
D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005472:Fluorouracil / Q000378:metabolism / Q000494:pharmacology*; D006498:Hepatectomy; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008115:Liver Regeneration / Q000187:drug effects*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D013385:Succinate Dehydrogenase; D005472:Fluorouracil