The effects of 5-fluorouridine, 5-fluorodeoxyuridine, and 5-fluorodeoxyuridine monophosphate on rabbit tenon's capsule fibroblasts in vitro.
Inhibition of rabbit subconjunctival fibroblast attachment and proliferation by 5-fluorouridine (FUR), 5-fluoro-2 deoxyuridine (FUdR), and 5-fluoro-2-deoxyuridine-5-monophosphate (FdUMP), was determined by 3H-adenosine uptake, cell counting, and colorimetric assays for the concentration range of 1000 to 0.0001 micrograms/ml over an 9 day period. The mean 50% inhibitory doses against proliferation were calculated for each assay. Rabbit fibroblast attachment was not inhibited at any drug concentration by either FUR, FUdR, or FdUMP. For rabbit fibroblast proliferation, FUR was found to be 10-100 fold more potent than FUdR and FdUMP. When comparing the human and rabbit cells, the unpaired t-test analysis showed no consistent statistical difference of the ID50s for FUR, FUdR or FdUMP. Rabbit ocular fibroblasts may be useful in modeling the proliferation of human ocular fibroblasts. These in vitro results may be useful for predicting optimal drug dosages for future in vivo testing of these drugs.
Smyth
R J
RJ
Department of Ophthalmology, Jules Stein Eye Institute, UCLA School of Medicine.
Moore
J J
JJ
Shapourifar-Tehrani
S
S
Lee
D A
DA
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004247:DNA / Q000096:biosynthesis; D005205:Fascia / Q000166:cytology / Q000187:drug effects*; D005347:Fibroblasts / Q000187:drug effects*; D005467:Floxuridine / Q000494:pharmacology*; D006801:Humans; D011817:Rabbits; D014529:Uridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001619:beta-N-Acetylhexosaminidases / Q000378:metabolism
D005467:Floxuridine; C001943:5-fluorouridine; D004247:DNA; D001619:beta-N-Acetylhexosaminidases; D000241:Adenosine; D014529:Uridine