The long-term effects of 5-fluorouracil and sodium butyrate on human Tenon's fibroblasts.
The use of subconjunctival 5-fluorouracil (5-FU) in the first weeks after filtration surgery may ensure long-term bleb survival despite a continuing proliferative stimulus such as in eyes with neovascular glaucoma. In addition, long-term side effects may occur, such as increasing bleb thinning. To ascertain the long-term effects of 5-FU and sodium butyrate, an agent with differentiating and antiproliferative properties, we exposed proliferating human Tenon's capsule fibroblasts to different concentrations of the drugs. The cells were exposed to 5-FU for 1-12 d. The cells were subsequently observed for up to 30 d. Cell proliferation was assessed using cell counting and bromodeoxyuridine uptake, and cell viability was assessed with trypan blue uptake. 5-FU and sodium butyrate inhibited fibroblast proliferation during the treatment period. Higher concentrations of 5-FU (100 and 1000 micrograms/ml) for as little as 1 d resulted in no significant increase in the number of fibroblasts for at least 29 d after treatment was stopped, despite continued stimulation with serum. When treatment with sodium butyrate was stopped, there was greater recovery of proliferation. At a constant concentration of 1000 micrograms/ml of 5-FU for 3 or more days, or a concentration of 100 mmol/l sodium butyrate for 12 d, the entire fibroblast population gradually died over the 30 d period. Thus, short-term treatment with 5-FU may result in long-term inhibition of proliferation of fibroblasts. Long-term inhibition depends on the duration of treatment or on the concentration of 5-FU. Short-term treatment may be affecting the ability of the tissues at the bleb site to heal in the long term. Different dosage regimens may have advantages and are discussed.
Khaw
P T
PT
Institute of Ophthalmology, London, England.
Ward
S
S
Porter
A
A
Grierson
I
I
Hitchings
R A
RA
Rice
N S
NS
D000293:Adolescent; D001973:Bromodeoxyuridine / Q000378:metabolism; D002087:Butyrates / Q000494:pharmacology*; D020148:Butyric Acid; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D005123:Eye / Q000166:cytology / Q000187:drug effects; D005205:Fascia / Q000166:cytology; D005347:Fibroblasts / Q000187:drug effects* / Q000378:metabolism; D005472:Fluorouracil / Q000494:pharmacology*; D006801:Humans; D008137:Longitudinal Studies
D002087:Butyrates; D020148:Butyric Acid; D001973:Bromodeoxyuridine; D005472:Fluorouracil