Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.
BACKGROUND
Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. The tight skin (TSK) mouse has skin which, in some respects, mimics that of patients with scleroderma. The skin radiation response of TSK mice has not been previously reported. If TSK mice are shown to have radiation sensitive skin, they may prove to be a useful model to examine the mechanisms underlying skin radiation injury, protection, mitigation and treatment.


METHODS
The hind limbs of TSK and parental control C57BL/6 mice received a radiation exposure sufficient to cause approximately the same level of acute injury. Endpoints included skin damage scored using a non-linear, semi-quantitative scale and tissue fibrosis assessed by measuring passive leg extension. In addition, TGF-beta1 cytokine levels were measured monthly in skin tissue.


RESULTS
Contrary to our expectations, TSK mice were more resistant (i.e. 20%) to radiation than parental control mice. Although acute skin reactions were similar in both mouse strains, radiation injury in TSK mice continued to decrease with time such that several months after radiation there was significantly less skin damage and leg contraction compared to C57BL/6 mice (p < 0.05). Consistent with the expected association of transforming growth factor beta-1 (TGF-beta1) with late tissue injury, levels of the cytokine were significantly higher in the skin of the C57BL/6 mouse compared to TSK mouse at all time points (p < 0.05).


CONCLUSIONS
TSK mice are not recommended as a model of scleroderma involving radiation injury. The genetic and molecular basis for reduced radiation injury observed in TSK mice warrants further investigation particularly to identify mechanisms capable of reducing tissue fibrosis after radiation injury.
Kumar
Sanath
S
Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA. skumar4@hfhs.org
Kolozsvary
Andrew
A
Kohl
Robert
R
Lu
Mei
M
Brown
Stephen
S
Kim
Jae Ho
JH
D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis / Q000209:etiology* / Q000473:pathology; D006579:Heterozygote; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011832:Radiation Injuries / Q000209:etiology*; D018787:Radiation Oncology / Q000379:methods; D011878:Radiotherapy / Q000009:adverse effects*; D012594:Scleroderma, Localized / Q000209:etiology*; D015398:Signal Transduction; D012867:Skin / Q000293:injuries* / Q000378:metabolism / Q000528:radiation effects*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D053773:Transforming Growth Factor beta1