Modulation of skin collagen metabolism by irradiation: collagen synthesis is increased in irradiated human skin

Radiation-induced fibrosis is a common side-effect of cancer treatment, The pathophysiological events leading to fibrosis are not known in detail. We analysed the effect of therapeutic irradiation on human skin collagen synth esis, skin thickness, gelatinases and their inhibitors. Twenty randomly cho sen women who had been treated for breast cancer with surgery and radiation therapy participated in the study In each patient, the irradiated skin are a was compared with a corresponding non-treated skin area. Suction blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptid es of type I and type III procollagens (PINP and PIIINP), tissue inhibitors of matrix metalloproteinases (MMPs) 1 and 2 (TIRMP-1 and TIMP-2) and MMP-9 and MMP-3/TIMP-2 complex, Skin biopsies were analysed for PINP and immunoh istochemical staining was used for PIIINP. In irradiated skin, PMP, PIIINP, TIMP-1 and MMP-2/TIMP-7 complex levels in SBF and the number of PINP-posit ive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of TIMP-2 in irradiated and non-irradiate d skin were similar, MMP-9 could not be detected in SBF with the assay used . The serum levels of MMP-9 were higher in the treated subjects than the re ference values. The serum values of PINP, PIIINP, TIMP-1, TIMP-2 and MMP-2/ TIMP-2 complex were not significantly affected. These results indicate incr eased local collagen synthesis and accumulation of connective tissue in irr adiated skin. The marked upregulation of collagen synthesis as a result of irradiation offers a possibility to treat this complication with compounds such as topical steroids which downregulate collagen synthesis.