Illsley M C, Peacock J H, McAnulty R J, Yarnold J R
Institute of Cancer Research, Cotswold Road, Sutton, Surrey, SM2 5NG, UK.
Br J Cancer. 2000 Sep;83(5):650-4. doi: 10.1054/bjoc.2000.1321.
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.
正常组织中的纤维化是许多癌症部位放疗常见的剂量限制性晚期并发症，但其发病机制尚不清楚。我们进行了一项对照研究，观察放疗对取自接受放疗患者皮肤活检样本所培养的成纤维细胞胶原蛋白生成的影响。使用300 kV X射线单次给予8 Gy剂量照射八周后，五名在皇家马斯登医院接受治疗的患者接受了照射部位及对侧未照射身体部位的活检。将照射部位和对照未照射部位的成纤维细胞进行体外培养，并在标准化条件下，于有和没有1 ng/ml转化生长因子β(1)（TGFβ(1)）存在的情况下孵育48小时，期间使用高效液相色谱法测量胶原蛋白生成率。照射皮肤所培养的细胞中胶原蛋白生成增加；照射细胞中胶原蛋白生成率中位数为61.16皮摩尔羟脯氨酸/10⁵细胞/小时，未照射细胞中为39.78皮摩尔羟脯氨酸/10⁵细胞/小时，P = 0.016（曼-惠特尼U检验）。在未照射部位的成纤维细胞中，添加TGFβ(1)可增加胶原蛋白生成率；然而，在照射部位所培养的三个细胞系中未观察到TGFβ(1)对胶原蛋白生成的这种作用。
