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2 July 2013 Quercetin Inhibits Radiation-Induced Skin Fibrosis
Jason A. Horton, Fei Li, Eun Joo Chung, Kathryn Hudak, Ayla White, Kristopher Krausz, Frank Gonzalez, Deborah Citrin
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Radiation induced fibrosis of the skin is a late toxicity that may result in loss of function due to reduced range of motion and pain. The current study sought to determine if oral delivery of quercetin mitigates radiation-induced cutaneous injury. Female C3H/HeN mice were fed control chow or quercetin-formulated chow (1% by weight). The right hind leg was exposed to 35 Gy of X rays and the mice were followed serially to assess acute toxicity and hind leg extension. Tissue samples were collected for assessment of soluble collagen and tissue cytokines. Human and murine fibroblasts were subjected to clonogenic assays to determine the effects of quercetin on radiation response. Contractility of fibroblasts was assessed with a collagen contraction assay in the presence or absence of quercetin and transforming growth factor-β (TGF-β). Western blotting of proteins involved in fibroblast contractility and TGF-β signaling were performed. Quercetin treatment significantly reduced hind limb contracture, collagen accumulation and expression of TGF-β in irradiated skin. Quercetin had no effect on the radioresponse of fibroblasts or murine tumors, but was capable of reducing the contractility of fibroblasts in response to TGF-β, an effect that correlated with partial stabilization of phosphorylated cofilin. Quercetin is capable of mitigating radiation induced skin fibrosis and should be further explored as a therapy for radiation fibrosis.

Jason A. Horton, Fei Li, Eun Joo Chung, Kathryn Hudak, Ayla White, Kristopher Krausz, Frank Gonzalez, and Deborah Citrin "Quercetin Inhibits Radiation-Induced Skin Fibrosis," Radiation Research 180(2), 205-215, (2 July 2013).
Received: 26 October 2012; Accepted: 1 March 2013; Published: 2 July 2013
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