Type I collagen turnover and cross-linking are increased in irradiated skin of breast cancer patients

Background and purpose: The effects of radiation therapy on the turnover an d structure of type I collagen were studied in irradiated and contralateral skin of 18 breast cancer patients without clinically evident fibrosis. Materials and methods: The rates of on-going type I collagen synthesis and degradation were assessed by the aminoterminal propeptide of type I procoll agen (PINP) and by two different assays (ICTP and SP4) for the carboxytermi nal telopeptide of type I collagen in the soluble tissue extracts, respecti vely. Also, TIMP-1, TIMP-2 and the MMP-2/TIMP-2 complex were measured in th e tissue extracts. Insoluble skin matrices, containing the cross-linked typ e I collagen fibres, were heat-denatured and digested with trypsin. Then, t he variants of the carboxyterminal telopeptide of type I collagen were sepa rated by high performance liquid chromatography (HPLC). The major histidino hydroxylysinonorleucine (HHL)-cross-linked variant was quantified by the SP 4 assay, and the minor pyridinoline analogue (PA)-cross-linked telopeptide was quantified by the ICTP assay. Results: Both the synthesis and degradation of type I collagen were increas ed (r = 0.906; P < 0.001) on the irradiated side, whereas the concentration of the MMP-2/TIMP-2 complex was decreased. In the insoluble tissue digests , the HHL-cross-linked telopeptides of type I collagen, also, when expresse d/tissue hydroxyproline, were increased in the irradiated skin. TIMP-1, TIM P-2 or PA-cross-linked telopeptides of type I collagen showed no difference s between the two sides. Conclusions: Radiotherapy induces a long-term increase in the turnover of t ype I collagen and leads to the accumulation of cross-linked type I collage n in skin. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.