In vitro analysis of radiation-induced dermal wounds.
OBJECTIVE
To investigate the pathophysiology of radiation-induced wounds of the head and neck at a molecular level.


METHODS
Basic science, prospective study.


METHODS
The study was conducted at the Department of Otolaryngology-Head and Neck Surgery, Ruprecht Karls-University Heidelberg, Faculty of Medicine Mannheim, Mannheim, Germany.


METHODS
Keratinocytes from chronic nonhealing ulcers in irradiated areas as well as from healthy skin areas in the same patients (n = 3) were harvested during surgical procedures and isolated in cell culture. First, a proliferation assay was performed. Gene expression was analyzed by microarray, protein expression by immunohistochemistry.


RESULTS
Keratinocytes from radiogenic wounds showed a shift from the high molecular keratins 1 and 10 to the low molecular keratins 5 and 14 compared to normal control skin. Keratinocytes from nonhealing wounds showed a decreased expression of transforming growth factor alpha and beta 1, fibroblast growth factor 1 and 2, keratinocyte growth factor, vascular endothelial growth factor, and hepatocyte growth factor. The matrix metalloproteinases 2, 12, and 13 showed increased expression in irradiated keratinocytes and fibroblasts.


CONCLUSIONS
Our data showed a change of keratinocytes to a less differentiated state due to radiation. Additionally, it seems that radiation-induced dermal injuries often fail to heal because of decreased proliferation, impaired angiogenesis, and persistently high concentrations of matrix metalloproteinases.
Goessler
Ulrich Reinhart
UR
Department of Otolaryngology-Head and Neck Surgery, Ruprecht Karls-University Heidelberg, Faculty of Medicine Mannheim, Mannheim, Germany. ugoessler@web.de
Bugert
Peter
P
Kassner
Stefan
S
Stern-Straeter
Jens
J
Bran
Gregor
G
Sadick
Haneen
H
Hörmann
Karl
K
Riedel
Frank
F
D002294:Carcinoma, Squamous Cell / Q000532:radiotherapy / Q000601:surgery; D002454:Cell Differentiation / Q000528:radiation effects; D054885:Cumulus Cells; D016207:Cytokines / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000532:radiotherapy / Q000601:surgery; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects*; D020782:Matrix Metalloproteinases / Q000032:analysis; D020411:Oligonucleotide Array Sequence Analysis; D011446:Prospective Studies; D011832:Radiation Injuries / Q000503:physiopathology*; D012867:Skin / Q000528:radiation effects; D017695:Soft Tissue Injuries / Q000503:physiopathology; D014456:Ulcer / Q000503:physiopathology*; D014945:Wound Healing / Q000502:physiology*
D016207:Cytokines; D020782:Matrix Metalloproteinases