Abstract
BackgroundRadiation 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.MethodsThe 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-β1 cytokine levels were measured monthly in skin tissue.ResultsContrary 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-β1) 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).ConclusionTSK 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.
Highlights
Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis
Skin injuries up to six weeks following 60 Gy (2 fractions of 30 Gy separated by 24 hours) and 50 Gy (2 fractions of 25 Gy separated by 24 hours) were comparable in tight skin (TSK) and C57BL/6 strains respectively (Fig 1a)
This translates into a radiation protection factor of 1.2 for TSK mouse
Summary
Radiation therapy is generally contraindicated for cancer patients with collagen vascular diseases (CVD) such as scleroderma due to an increased risk of fibrosis. Radiation fibrosis is frequently seen in patients undergoing high dose curative radiotherapy. It has been described in many tissues, including skin [1], lung [2]. Collagen vascular disease (CVD) patients, with scleroderma, are believed to be at increased risk of (page number not for citation purposes). The increased toxicity is a serious clinical problem as many of these patients need radiation frequently as a part of cancer treatment and during breast conservation therapy for better cosmesis. An abnormal increase in tissue TGF-β1 after radiation may underlie excessive fibrosis seen in CVD patients. Understanding the dynamics of TGF-β1 regulation after radiation in the setting CVD may be helpful in decreasing the long term toxicities associated with radiation therapy
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