Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis
Abstract Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis e...
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Nature Portfolio
2024-10-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-76021-9 |
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| author | Jessica Lawrence Davis Seelig Kimberly Demos-Davies Clara Ferreira Yanan Ren Li Wang Sk. Kayum Alam Rendong Yang Alonso Guedes Angela Craig Luke H. Hoeppner |
| author_facet | Jessica Lawrence Davis Seelig Kimberly Demos-Davies Clara Ferreira Yanan Ren Li Wang Sk. Kayum Alam Rendong Yang Alonso Guedes Angela Craig Luke H. Hoeppner |
| author_sort | Jessica Lawrence |
| collection | DOAJ |
| description | Abstract Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury. |
| format | Article |
| id | doaj-art-60fa46210bd04a829af4e25c508b4ca1 |
| institution | OA Journals |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-60fa46210bd04a829af4e25c508b4ca12025-08-20T02:11:18ZengNature PortfolioScientific Reports2045-23222024-10-0114111310.1038/s41598-024-76021-9Radiation dermatitis in the hairless mouse model mimics human radiation dermatitisJessica Lawrence0Davis Seelig1Kimberly Demos-Davies2Clara Ferreira3Yanan Ren4Li Wang5Sk. Kayum Alam6Rendong Yang7Alonso Guedes8Angela Craig9Luke H. Hoeppner10Department of Veterinary Clinical Sciences, College of Veterinary Medicine, University of MinnesotaDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of MinnesotaDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of MinnesotaDepartment of Radiation Oncology, Medical School, University of MinnesotaThe Hormel Institute, University of MinnesotaThe Hormel Institute, University of MinnesotaThe Hormel Institute, University of MinnesotaThe Hormel Institute, University of MinnesotaDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of MinnesotaDepartment of Veterinary Clinical Sciences, College of Veterinary Medicine, University of MinnesotaMasonic Cancer Center, University of MinnesotaAbstract Over half of all people diagnosed with cancer receive radiation therapy. Moderate to severe radiation dermatitis occurs in most human radiation patients, causing pain, aesthetic distress, and a negative impact on tumor control. No effective prevention or treatment for radiation dermatitis exists. The lack of well-characterized, clinically relevant animal models of human radiation dermatitis contributes to the absence of strategies to mitigate radiation dermatitis. Here, we establish and characterize a hairless SKH-1 mouse model of human radiation dermatitis by correlating temporal stages of clinical and pathological skin injury. We demonstrate that a single ionizing radiation treatment of 30 Gy using 6 MeV electrons induces severe clinical grade 3 peak toxicity at 12 days, defined by marked erythema, desquamation and partial ulceration, with resolution occurring by 25 days. Histopathology reveals that radiation-induced skin injury features temporally unique inflammatory changes. Upregulation of epidermal and dermal TGF-ß1 and COX-2 protein expression occurs at peak dermatitis, with sustained epidermal TGF-ß1 expression beyond resolution. Specific histopathological variables that remain substantially high at peak toxicity and early clinical resolution, including epidermal thickening, hyperkeratosis and dermal fibroplasia/fibrosis, serve as specific measurable parameters for in vivo interventional preclinical studies that seek to mitigate radiation-induced skin injury.https://doi.org/10.1038/s41598-024-76021-9TranslationalDermatitisRadiationSkinInflammationTGF-ß1 |
| spellingShingle | Jessica Lawrence Davis Seelig Kimberly Demos-Davies Clara Ferreira Yanan Ren Li Wang Sk. Kayum Alam Rendong Yang Alonso Guedes Angela Craig Luke H. Hoeppner Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis Scientific Reports Translational Dermatitis Radiation Skin Inflammation TGF-ß1 |
| title | Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| title_full | Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| title_fullStr | Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| title_full_unstemmed | Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| title_short | Radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| title_sort | radiation dermatitis in the hairless mouse model mimics human radiation dermatitis |
| topic | Translational Dermatitis Radiation Skin Inflammation TGF-ß1 |
| url | https://doi.org/10.1038/s41598-024-76021-9 |
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