Effect of gemcitabine on acute and late radiation toxicity of skin and underlying soft tissues to single-dose irradiation in a nude mice model.
OBJECTIVE
To investigate the influence of gemcitabine (GEM) on acute and late toxicity of radiotherapy (XRT) in an in vivo model of acute skin reactions and late fibrotic sequelae of skin and underlying soft tissues.


METHODS
Single-fraction XRT was applied to the right hind leg of nude mice under ambient conditions. Single-dose GEM was applied i.p. (550 mg/kg body weight). In a first set of experiments, the influence of timing of chemotherapy relative to the onset of irradiation was investigated with GEM application 36, 24, and 2 h before and 24 h subsequent to 40 Gy XRT. With a fixed interval between chemotherapy and XRT taken from these studies, the dose-response relationship was examined for XRT in the range of 20-65 Gy. Control mice were irradiated without GEM treatment. Using a scoring system, onset, duration, and extent of acute skin reactions were analyzed. Skin fibrosis was measured by intracutaneous ink-mark separation. Soft tissue fibrosis was assessed using the leg contracture assay. ED50 calculations were performed for extent of acute and late reactions.


RESULTS
Timing of GEM application relative to XRT had no significant influence on acute skin reactions or on fibrotic changes. Onset, duration, and extent of acute skin toxicity, as well as skin and leg contracture, were not significantly modulated by GEM in the dose-response experiments with GEM applied 2 h before XRT.


CONCLUSIONS
Acute and late toxicity of skin and underlying soft tissues is not significantly increased after single-fraction radiotherapy in combination with GEM in the nude mice model.
Classen
Johannes
J
Department of Radiation Oncology, Tuebingen University, Hoppe-Seyler-Strasse 3, D-72074 Tuebingen, Germany. johannes.classen@med.uni-tuebingen.de
Paulsen
Frank
F
Hehr
Thomas
T
Bamberg
Michael
M
Budach
Wilfried
W
D000818:Animals; D003238:Connective Tissue / Q000187:drug effects / Q000528:radiation effects; D003841:Deoxycytidine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004307:Dose-Response Relationship, Radiation; D005355:Fibrosis; D051379:Mice; D008819:Mice, Nude; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D012867:Skin / Q000187:drug effects / Q000473:pathology / Q000528:radiation effects*; D013997:Time Factors; D000093542:Gemcitabine
D011838:Radiation-Sensitizing Agents; D003841:Deoxycytidine; D000093542:Gemcitabine