Consequences of ornithine decarboxylase inactivation by alpha-difluoromethylornithine and 5-fluorouracil on the growth of rabbit fibroblasts.
The role of ornithine decarboxylase and polyamines in proliferative vitreoretinopathy (PVR) is ill-defined. An increase in the activity of this enzyme concurrent with an increase in polyamine levels may be essential in the process of intraocular cellular proliferation. Therefore, in this study, cultured rabbit fibroblasts were exposed to DL-alpha-difluoromethylornithine (alpha-DFMO), a mechanism-based irreversible inactivator of ornithine decarboxylase, alone and in combination with 5-fluorouracil (5-FU). Concentrations of 0.1mM alpha-DFMO and 0.125mM 5-FU decreased rabbit fibroblast cell number by 60% and 65%, respectively, after three days, while with either 5.0mM alpha-DFMO or 0.25mM 5-FU, cell number is decreased by 95%. The effectiveness of inhibitory concentrations of 5-FU and alpha-DFMO together in reducing cell number is additive.
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D000518:Eflornithine; D004789:Enzyme Activation / Q000187:drug effects; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects; D005472:Fluorouracil / Q000494:pharmacology*; D009952:Ornithine / Q000031:analogs & derivatives* / Q000494:pharmacology; D065108:Ornithine Decarboxylase Inhibitors; D011817:Rabbits; D012867:Skin / Q000166:cytology* / Q000187:drug effects
D065108:Ornithine Decarboxylase Inhibitors; D009952:Ornithine; D005472:Fluorouracil; D000518:Eflornithine