The effect of mitomycin on extracellular matrix proteins in a rat wound model.
OBJECTIVE
To evaluate the effect of topical and injected mitomycin on the expression of extracellular matrix proteins by fibroblasts in an early surgical wound model.


METHODS
A prospective, controlled study in a rat wound model.


METHODS
Six linear incisions were placed on the backs of each of three Sprague-Dawley rats, and polyvinyl alcohol sponges were implanted. Two control wounds were implanted with saline-soaked sponges. The two topical test group wounds were treated with 0.5 mg/mL topical mitomycin for 2 minutes, followed by sponge implantation. The two injection test group wounds were injected with 0.3 mL mitomycin (0.5 mg/mL) before incision and sponge implantation. Each incision was closed uniformly with 3-0 nylon suture. The sponges were harvested on the tenth postoperative day. Fibroblasts that had grown into the sponges were separated, and polymerase chain reaction analysis was used to quantify the expression of messenger RNA for several extracellular matrix proteins.


RESULTS
The expression of mRNA for some extracellular matrix proteins (elastase, hyaluronidase, and procollagen) was downregulated in the mitomycin test groups. The effect was more pronounced in the topical mitomycin test group compared with the injection test group. The wounds in the topical group were prone to dehiscence, and the wounds in the injection group demonstrated poor healing when compared with controls.


CONCLUSIONS
Mitomycin may inhibit wound healing by downregulating the gene expression for extracellular matrix proteins. This effect may be selective and may be more pronounced on inducible genes. Such findings prompt further studies regarding possible "best time" windows and selective gene suppression. The use of mitomycin may be limited in situations where wound integrity is necessary.
Gray
Steven D
SD
Division of Otolaryngology-Head and Neck Surgery, University of Utah Medical Center, Salt Lake City, Utah, USA.
Tritle
Nathan
N
Li
Wenhua
W
D000287:Administration, Topical; D000818:Animals; D015536:Down-Regulation; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D015870:Gene Expression / Q000187:drug effects*; D007267:Injections; D008297:Male; D016685:Mitomycin / Q000008:administration & dosage / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D016326:Extracellular Matrix Proteins; D012333:RNA, Messenger; D016685:Mitomycin