Limits...
Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.

Kumar S, Kolozsvary A, Kohl R, Lu M, Brown S, Kim JH - Radiat Oncol (2008)

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA. skumar4@hfhs.org

ABSTRACT

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).

Conclusion: 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.

Show MeSH

Related in: MedlinePlus

Photograph of representative irradiated leg of TSK mice showing minor damage 110 days post-irradiation compared to parental control. The TSK mice had relatively normal legs (panel B) post-irradiation except for hair loss whereas parental control mice (panel A) showed extensive skin and leg injuries following the radiation exposure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC2599892&req=5

Figure 3: Photograph of representative irradiated leg of TSK mice showing minor damage 110 days post-irradiation compared to parental control. The TSK mice had relatively normal legs (panel B) post-irradiation except for hair loss whereas parental control mice (panel A) showed extensive skin and leg injuries following the radiation exposure.

Mentions: Our results evidently demonstrate that TSK mice are resistant to radiation injury compared with the parental C57BL/6 strain with respect to the manifestation of late skin injury and fibrosis (Fig. 3). Even though both the TSK mice and control mice showed similar degrees of skin damage initially, the injury in TSK mice healed promptly and ultimately exhibited signs of less fibrosis. This study is the first report on the effects of radiation in an animal model for scleroderma.


Radiation-induced skin injury in the animal model of scleroderma: implications for post-radiotherapy fibrosis.

Kumar S, Kolozsvary A, Kohl R, Lu M, Brown S, Kim JH - Radiat Oncol (2008)

Photograph of representative irradiated leg of TSK mice showing minor damage 110 days post-irradiation compared to parental control. The TSK mice had relatively normal legs (panel B) post-irradiation except for hair loss whereas parental control mice (panel A) showed extensive skin and leg injuries following the radiation exposure.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2599892&req=5

Figure 3: Photograph of representative irradiated leg of TSK mice showing minor damage 110 days post-irradiation compared to parental control. The TSK mice had relatively normal legs (panel B) post-irradiation except for hair loss whereas parental control mice (panel A) showed extensive skin and leg injuries following the radiation exposure.
Mentions: Our results evidently demonstrate that TSK mice are resistant to radiation injury compared with the parental C57BL/6 strain with respect to the manifestation of late skin injury and fibrosis (Fig. 3). Even though both the TSK mice and control mice showed similar degrees of skin damage initially, the injury in TSK mice healed promptly and ultimately exhibited signs of less fibrosis. This study is the first report on the effects of radiation in an animal model for scleroderma.

Bottom Line: 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.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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Radiation Oncology, Henry Ford Health System, Detroit, MI, USA. skumar4@hfhs.org

ABSTRACT

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).

Conclusion: 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.

Show MeSH
Related in: MedlinePlus