Time and dose effects of mitomycin C on extracellular matrix fibroblasts and proteins.
OBJECTIVE
The objective was to determine treatment dose and time-dependent effects of injected mitomycin C on extracellular matrix fibroblasts, collagen, and fibronectin, important mediators in the wound healing response, in a rat cutaneous wound model.


METHODS
A prospective, controlled animal study.


METHODS
Forty rats were injected with three different doses (0.4, 2.3, and 5.0 mg/mL) of mitomycin C at three different wound sites with a fourth wound site receiving saline as a control. The rats were grouped to have their tissue harvested at five different dates ranging from 1 week to 8 weeks. After death, samples from the wound site underwent Western blot analysis for collagen and fibronectin and histological analysis measuring fibroblast apoptosis.


RESULTS
Over an 8-week period, collagen and fibronectin significantly decreased and fibroblast apoptosis significantly increased. No correlation was found between the injected dose of mitomycin C and either the extracellular matrix protein concentration or the rate of fibroblast apoptosis.


CONCLUSIONS
Mitomycin C demonstrated a long-term effect in a wound, inhibiting collagen and fibronectin production and inducing apoptosis. Use of mitomycin C in excess of 0.4 mg/mL did not alter protein concentrations or rate of apoptosis.
Ferguson
Bryce
B
Division of Otolaryngology-Head and Neck Surgery, School of Medicine, University of Utah, Salt Lake City, UT 84132, USA.
Gray
Steven D
SD
Thibeault
Susan
S
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D003094:Collagen / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000187:drug effects*; D005353:Fibronectins / Q000187:drug effects / Q000378:metabolism*; D020287:In Situ Nick-End Labeling; D008297:Male; D016685:Mitomycin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D005353:Fibronectins; D016685:Mitomycin; D003094:Collagen