Increased collagen production in fibroblasts cultured from irradiated skin and effect of TGF β ₁– clinical study

Abstract

Fibrosis in normal tissues is a common and dose-limiting late complication of radiotherapy at many cancer sites, but its pathogenesis is poorly understood. We undertook a controlled study of the effect of irradiation on the collagen production of fibroblasts cultured from skin biopsies taken from patients undergoing radiotherapy treatment. Eight weeks after a single 8 Gy fraction using 300 kV X-rays, five patients treated at the Royal Marsden Hospital underwent biopsy of the irradiated site and of the contralateral, unirradiated body site. Fibroblasts from irradiated and control, unirradiated sites were cultured in vitro, and collagen production rates were measured during a 48-hour incubation under standardized conditions and in the presence and absence of transforming growth factor β₁(TGF β₁), 1 ng/ml, using HPLC. Collagen production was elevated in cells cultured from irradiated skin; median collagen production rates 61.16 pmoles hydroxyproline/10⁵cells/hour in irradiated cells, 39.78 pmoles hydroxyproline/10⁵cells/hour in unirradiated cells, P = 0.016 (Mann–Whitney U-test). In fibroblasts from unirradiated sites, collagen production rates were increased by the addition of TGF β₁; however, in three of the cell lines cultured from irradiated sites this effect of TGF β₁on collagen production was not observed. © 2000 Cancer Research Campaign