Studies of the in vivo radiosensitivity of human skin fibroblasts

• Published in: Radiotherapy and oncology Vol. 84; no. 1; pp. 75 - 83
• Main Authors: Hill, Richard P, Kaspler, Pavel, Griffin, Anthony M, O’Sullivan, Brian, Catton, Charles, Alasti, Hamideh, Abbas, Ahmar, Heydarian, Moustafa, Ferguson, Peter, Wunder, Jay S, Bell, Robert S
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.07.2007
• Subjects: Adult; Aged; Aged, 80 and over; Bystander effects; DNA Damage; Dose Fractionation; Female; Fibroblasts; Fibroblasts - radiation effects; Hematology, Oncology and Palliative Medicine; Humans; Male; Micronuclei; Middle Aged; Radiation Tolerance; Radiosensitivity in situ; Radiotherapy, Adjuvant; Sarcoma - radiotherapy; Sarcoma - surgery; Skin Neoplasms - radiotherapy; Skin Neoplasms - surgery; Wound healing; Wound Healing - radiation effects; Fibroblasts; Bystander effects; Wound healing; Micronuclei; Radiosensitivity in situ
• ISSN: 0167-8140; 1879-0887
• DOI: 10.1016/j.radonc.2007.05.025

Abstract Background and purpose 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 – 50 Gy 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.