Transcription of liver ribosomal RNA: differential effect of 5-fluorouracil depending on the nutritional state of mice.
The effect of 5-fluorouracil (5-FUra) on RNA transcription in mice liver cells was studied using animals exposed to different nutritional conditions as a model of normal, nondividing cells. There are two levels of rRNA transcription in mouse liver: a basal level found in mice fed on a complete diet (control mice) and a higher level, two- to three-fold increased over the basal, found in mice fed on a protein-depleting diet for about 3 days and refed on a complete diet for at least 5 hr (refed mice). The rRNA transcription was measured as the activity of RNA polymerase I in isolated liver nuclei. It was found that the intraperitoneal administration of 5-FUra (30 mg/kg body wt) to refed mice rapidly decreases the higher level of rRNA transcription towards the basal level. This is accomplished through a decrease of the initiation frequency of rRNA chains by RNA polymerase I. 5-FUra however, does not affect the basal level of rRNA transcription in liver from mice fed on a complete diet. Under this condition the drug does not affect the initiation frequency of rRNA chains. The effect of 5-FUra on rRNA transcription in refed mice is not mediated by an inhibition of protein synthesis.
D000818:Animals; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D005472:Fluorouracil / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D009752:Nutritional Status / Q000187:drug effects*; D012318:RNA Polymerase I / Q000378:metabolism*; D012335:RNA, Ribosomal / Q000187:drug effects / Q000235:genetics*; D014158:Transcription, Genetic / Q000187:drug effects*; D014544:Uridine Triphosphate / Q000378:metabolism
D012335:RNA, Ribosomal; D012318:RNA Polymerase I; D005472:Fluorouracil; D014544:Uridine Triphosphate