The effect of 5-fluorouracil on Dupuytren fibroblast proliferation and differentiation.
BACKGROUND
Dupuytren's disease is a proliferative disease with contractile properties, prone to recur after surgery. Intra-operatively applied 5-fluorouracil has been used to avoid scar problems in the eye after glaucoma filtration surgery and was therefore investigated as a means to inhibit proliferation and myofibroblast differentiation in Dupuytren fibroblasts in vitro.


METHODS
Primary cell lines were obtained by explants from Dupuytren's tissue (n = 6), non-diseased palmar fascia from patients with Dupuytren's disease (n = 3) and carpal ligament from patients undergoing carpal tunnel release (n = 3). The effect of 5-fluorouracil on proliferation was assessed by cell counting. Myofibroblast differentiation, an intergral part of Dupuytren's contracture, was investigated by staining for alpha smooth muscle actin, a marker for contractile cells, using immunohisto-chemical methods.


RESULTS
A single exposure to 5-fluorouracil caused a sustained inhibition of proliferation in Dupuytren's and non-diseased fascia cultures, whilst the effect on carpal ligament cultures was transient. Untreated Dupuytren's fibroblasts exhibited the highest myofibroblast differentiation, whilst differentiation in non-diseased fascia cultures was shown to be proportional to cell density and virtually non-existent in carpal ligament cultures. After 5-fluorouracil exposure, the differentiation was significantly reduced in Dupuytren's fibroblasts cultures, reduced at high cell densities in non-diseased fascia and unchanged in carpal ligament cell cultures.


CONCLUSIONS
5-fluorouracil inhibits both proliferation and myofibroblast differentiation in Dupuytren's cell cultures and may have a potential use as an adjuvant treatment to Dupuytren surgery in order to reduce the rate of recurrence and contracture.
Jemec
B
B
Restoration of Appearance and Function Trust, Northwood, Middlesex, UK.
Linge
C
C
Grobbelaar
A O
AO
Smith
P J
PJ
Sanders
R
R
McGrouther
D A
DA
D000368:Aged; D000963:Antimetabolites / Q000494:pharmacology / Q000627:therapeutic use*; D016022:Case-Control Studies; D002452:Cell Count / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004353:Drug Evaluation, Preclinical; D004387:Dupuytren Contracture / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology / Q000601:surgery; D005260:Female; D005347:Fibroblasts / Q000187:drug effects* / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009210:Myofibrils / Q000187:drug effects / Q000502:physiology; D012008:Recurrence
D000963:Antimetabolites; D005472:Fluorouracil