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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.

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Related in: MedlinePlus

Skin injury (panel A) and leg extension (panel B) in TSK (solid data points) and parental C57BL/6 mice (open data points) following 60 Gy (TSK) or 50 Gy (C57BL/6) given as two equal radiation fractions separated by 24 hours. Each point for skin injury represents the median value for the group. The error bars represent minimum and maximum value of the range. Each point for leg extension data represents mean value for the group. The error bars represent the standard deviation of the mean.
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Figure 1: Skin injury (panel A) and leg extension (panel B) in TSK (solid data points) and parental C57BL/6 mice (open data points) following 60 Gy (TSK) or 50 Gy (C57BL/6) given as two equal radiation fractions separated by 24 hours. Each point for skin injury represents the median value for the group. The error bars represent minimum and maximum value of the range. Each point for leg extension data represents mean value for the group. The error bars represent the standard deviation of the mean.

Mentions: Acute skin reactions were initially similar for the TSK and C57BL/6 parental mouse strains. For example, 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 TSK and C57BL/6 strains respectively (Fig 1a). This translates into a radiation protection factor of 1.2 for TSK mouse. In sharp contrast to the acute response, at between two months and three months after radiation, a differential response to radiation in the two strains was evident with TSK mice showing less skin damage compared to C57BL/6 mice (p < 0.05) (Fig 1a). C57BL/6 mice received lower radiation dose compared to TSK mice as they tend to develop severe damage after two fractions of 30 Gy.


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)

Skin injury (panel A) and leg extension (panel B) in TSK (solid data points) and parental C57BL/6 mice (open data points) following 60 Gy (TSK) or 50 Gy (C57BL/6) given as two equal radiation fractions separated by 24 hours. Each point for skin injury represents the median value for the group. The error bars represent minimum and maximum value of the range. Each point for leg extension data represents mean value for the group. The error bars represent the standard deviation of the mean.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 1: Skin injury (panel A) and leg extension (panel B) in TSK (solid data points) and parental C57BL/6 mice (open data points) following 60 Gy (TSK) or 50 Gy (C57BL/6) given as two equal radiation fractions separated by 24 hours. Each point for skin injury represents the median value for the group. The error bars represent minimum and maximum value of the range. Each point for leg extension data represents mean value for the group. The error bars represent the standard deviation of the mean.
Mentions: Acute skin reactions were initially similar for the TSK and C57BL/6 parental mouse strains. For example, 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 TSK and C57BL/6 strains respectively (Fig 1a). This translates into a radiation protection factor of 1.2 for TSK mouse. In sharp contrast to the acute response, at between two months and three months after radiation, a differential response to radiation in the two strains was evident with TSK mice showing less skin damage compared to C57BL/6 mice (p < 0.05) (Fig 1a). C57BL/6 mice received lower radiation dose compared to TSK mice as they tend to develop severe damage after two fractions of 30 Gy.

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