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 synthesis, skin thickness,
gelatinases and their inhibitors. Twenty randomly chosen women who had been treated for
breast cancer with surgery and
radiation therapy participated in the study. In each patient, the irradiated skin area was compared with a corresponding non-treated skin area. Suction
blister fluid (SBF) and serum samples were analysed for the aminoterminal propeptides of type I and type III procollagens (PINP and
PIIINP), tissue inhibitors of
matrix metalloproteinases (
MMPs) 1 and 2 (TIMP-1 and TIMP-2) and MMP-9 and
MMP-2/TIMP-2 complex. Skin biopsies were analysed for PINP and immunohistochemical staining was used for
PIIINP. In irradiated skin, PINP,
PIIINP,
TIMP-1 and
MMP-2/TIMP-2 complex levels in SBF and the number of PINP-positive fibroblasts in tissue sections were significantly higher in comparison with non-treated skin. The levels of
TIMP-2 in irradiated and non-irradiated 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 reference values. The serum values of PINP,
PIIINP,
TIMP-1,
TIMP-2 and
MMP-2/TIMP-2 complex were not significantly affected. These results indicate increased local
collagen synthesis and accumulation of connective tissue in irradiated 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.