Incorporation of 5-fluorouracil into hepatoma and normal tissue RNA at protein depletion in the rat.
OBJECTIVE
5-fluorouracil (5-FU) exerts its effects mainly by its incorporation into RNA and inhibition of DNA synthesis. Its toxicity may therefore be estimated by measuring its incorporation into RNA. Protein malnutrition has been considered to increase the toxicity of 5-FU.


METHODS
Rats with a hepatoma implanted into the liver were fed on either a 25% or a 0% casein diet for 1 week. On the last day, they were infused via the hepatic artery with a therapeutic dose of 3H-5-FU. Its incorporation into RNA was measured in hepatoma and several normal tissues.


RESULTS
Protein deprivation increased the incorporation of 5-FU into liver and intestinal RNA. Incorporation into hepatoma RNA did not increase significantly, but the ratio, liver/hepatoma RNA incorporation, remained unchanged.


CONCLUSIONS
Protein deprivation might increase the toxicity of 5-FU on liver and intestine.
Roos
G
G
Department of Pathology, University of Lund, University Hospital, Sweden.
Stenram
U
U
D000818:Animals; D004273:DNA, Neoplasm / Q000096:biosynthesis* / Q000187:drug effects; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D006499:Hepatic Artery; D007261:Infusions, Intra-Arterial; D008099:Liver / Q000378:metabolism; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000378:metabolism*; D051381:Rats
D004273:DNA, Neoplasm; D011506:Proteins; D012334:RNA, Neoplasm; D005472:Fluorouracil