Studies of the in vivo radiosensitivity of human skin fibroblasts.
OBJECTIVE
To examine the radiosensitivity of skin cells obtained directly from the irradiated skin of patients undergoing fractionated radiation treatment prior to surgery for treatment of soft tissue sarcoma (STS) and to determine if there was a relationship with the development of wound healing complications associated with the surgery post-radiotherapy.


METHODS
Micronucleus (MN) formation was measured in cells (primarily dermal fibroblasts) obtained from human skin at their first division after being removed from STS patients during post-radiotherapy surgery (2-9 weeks after the end of the radiotherapy). At the time of radiotherapy (planned tumor dose - 50Gy in 25 daily fractions) measurements were made of surface skin dose at predetermined marked sites. Skin from these sites was obtained at surgery and cell suspensions were prepared directly for the cytokinesis-blocked MN assay. Cultured strains of the fibroblasts were also established from skin nominally outside the edge of the radiation beam and DNA damage (MN formation) was examined following irradiation in vitro for comparison with the results from the in situ irradiations.


RESULTS
Extensive DNA damage (MN) was detectable in fibroblasts from human skin at extended periods after irradiation (2-9 weeks after the end of the 5-week fractionated radiotherapy). Analysis of skin receiving a range of doses demonstrated that the level of damage observed was dose dependent. There was no clear correlation between the level of damage observed after irradiation in situ and irradiation of cell strains in culture. Similarly, there was no correlation between the extent of MN formation following in situ irradiation and the propensity for the patient to develop wound healing complications post-surgery.


CONCLUSIONS
Despite the presence of DNA damage in dermal fibroblasts weeks after the end of the radiation treatment, there was no relationship between this damage and wound healing complications following surgery post-irradiation. These results suggest that factors other than the radiosensitivity of the skin fibroblasts likely also play a role in wound healing in deep wound sites associated with surgery for STS following radiation therapy.
Hill
Richard P
RP
Division of Applied Molecular Oncology, Ontario Cancer Institute/Princess Margaret Hospital, University Ave., Toronto, Ont., Canada M5G 2M9. hill@uhnres.utoronto.ca
Kaspler
Pavel
P
Griffin
Anthony M
AM
O'Sullivan
Brian
B
Catton
Charles
C
Alasti
Hamideh
H
Abbas
Ahmar
A
Heydarian
Moustafa
M
Ferguson
Peter
P
Wunder
Jay S
JS
Bell
Robert S
RS
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004249:DNA Damage; D019583:Dose Fractionation, Radiation; D005260:Female; D005347:Fibroblasts / Q000528:radiation effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011836:Radiation Tolerance; D018714:Radiotherapy, Adjuvant; D012509:Sarcoma / Q000532:radiotherapy* / Q000601:surgery; D012878:Skin Neoplasms / Q000532:radiotherapy* / Q000601:surgery; D014945:Wound Healing / Q000528:radiation effects*