Effects of 5-fluorouracil and mitomycin C on cultured rabbit subconjunctival fibroblasts.
The authors investigated effects of two antimetabolites, 5-fluorouracil (5-FU) and mitomycin C (MMC), on proliferation and motility of cultured rabbit subconjunctival fibroblasts. Both drugs caused dose-dependent inhibition of fibroblast proliferation. These effects were reversible at lower doses (0.33 mg/l of 5-FU, 1.0 X 10(-3) mg/l of MMC) and at an early stage of treatment, but became irreversible at higher doses or after longer treatment times. The degree of growth inhibition reached a plateau after 7 days of treatment. Neither drug altered fibroblast migration in the agarose droplet motility assay or on the intra-cytoplasmic actin distribution by epifluorescent-light microscopy. These results indicate that 5-FU and MMC inhibit subconjunctival fibroblast function predominantly by their effect on cell proliferation rather than on cell motility. The clinical implications of these results may possibly support the use of a much lower total dose of subconjunctival antimetabolite than used in the 5-FU clinical trial.
Yamamoto
T
T
Department of Ophthalmology, University of Michigan, Ann Arbor.
Varani
J
J
Soong
H K
HK
Lichter
P R
PR
D000199:Actins / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D003228:Conjunctiva / Q000166:cytology / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects*; D005472:Fluorouracil / Q000494:pharmacology*; D008297:Male; D008856:Microscopy, Fluorescence; D016685:Mitomycin; D008937:Mitomycins / Q000494:pharmacology*; D011817:Rabbits
D000199:Actins; D008937:Mitomycins; D016685:Mitomycin; D005472:Fluorouracil