Increased collagen production in fibroblasts cultured from irradiated skin and 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 understood. We undertook a controlled study of the effect of irradiation on the collagen production of fibroblasts cultured from skin biopsies taken from pa...

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Bibliographic Details
Published in:British journal of cancer 2000-09, Vol.83 (5), p.650-654
Main Authors: Illsley, M C, Peacock, J H, McAnulty, R J, Yarnold, J R
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Biopsy
Breast Neoplasms - radiotherapy
Cells, Cultured
Chromatography, High Pressure Liquid
Collagen - biosynthesis
Colonic Neoplasms - radiotherapy
Female
Fibroblasts - metabolism
Fibroblasts - radiation effects
Flow Cytometry
Humans
Lung Neoplasms - radiotherapy
Male
Middle Aged
Prostatic Neoplasms - radiotherapy
Skin - radiation effects
Time Factors
Transforming Growth Factor beta - pharmacology
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Summary: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 beta(1)(TGF beta(1)), 1 ng/ml, using HPLC. Collagen production was elevated in cells cultured from irradiated 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 addition of TGF beta(1); however, in three of the cell lines cultured from irradiated sites this effect of TGF beta(1)on collagen production was not observed.
ISSN:0007-0920
DOI:10.1054/bjoc.2000.1321