Increased collagen production in fibroblasts cultured from irradiated skinand effect of TGF beta(1) - clinical study

Fibrosis in normal tissues is a common and dose-limiting late complication of radiotherapy at many cancer sites, but its pathogenesis is poorly unders tood. We undertook a controlled study of the effect of irradiation on the c ollagen production of fibroblasts cultured from skin biopsies taken from pa tients undergoing radiotherapy treatment. Eight weeks after a single 8 Gy f raction using 300 kV X-rays, five patients treated at the Royal Marsden Hos pital underwent biopsy of the irradiated site and of the contralateral, uni rradiated body site. Fibroblasts from irradiated and control, unirradiated sites were cultured in vitro, and collagen production rates were measured d uring a 48-hour incubation under standardized conditions and in the presenc e and absence of transforming growth factor beta(1) (TGF beta(1)), 1 ng/ml, using HPLC. Collagen production was elevated in cells cultured from irradi ated skin; median collagen production rates 61.16 pmoles hydroxyproline/10( 5) cells/hour in irradiated cells, 39.78 pmoles hydroxyproline/10(5) cells/ hour in unirradiated cells, P = 0.016 (Mann-Whitney U-test). In fibroblasts from unirradiated sites, collagen production rates were increased by the a ddition of TGF beta(1); however, in three of the cell lines cultured from i rradiated sites this effect of TGF beta(1) on collagen production was not o bserved. (C) 2000 Cancer Research Campaign.