Herskind C, Johansen J, Bentzen S M, Overgaard M, Overgaard J, Bamberg M, Rodemann H P
Section of Radiobiology and Molecular Environmental Research, University of Tübingen, Germany.
Acta Oncol. 2000;39(3):383-8. doi: 10.1080/028418600750013159.
In order to acquire a better understanding of the mechanism of radiation-induced fibrosis, we studied the differentiation of normal skin fibroblasts cultured from breast cancer radiotherapy patients with different risk of fibrosis. The differentiation state of fibroblasts was characterized in clonal cultures using established cytomorphological criteria. Collagen synthesis was determined by 3H-proline incorporation into pepsin-resistant protein. Radiation-induced inactivation of fibroblasts was paralleled by an increase in terminally differentiated fibrocytes, demonstrating that premature terminal differentiation is an important response to irradiation of fibroblasts from radiotherapy patients. Surviving colony-forming fibroblasts showed a change in differentiation with an increase in the ratio L:E of progenitor fibroblasts in late (L) compared to early (E) differentiation states. Furthermore, increased collagen production was observed after irradiation. The results provide evidence supporting a role of terminal fibroblast differentiation in radiation-induced fibrosis and imply that the progenitor population surviving radiotherapy might be more prone to terminal differentiation than before radiotherapy.
为了更好地理解辐射诱导纤维化的机制，我们研究了从具有不同纤维化风险的乳腺癌放疗患者中培养的正常皮肤成纤维细胞的分化情况。使用既定的细胞形态学标准在克隆培养中对成纤维细胞的分化状态进行了表征。通过将3H-脯氨酸掺入耐胃蛋白酶的蛋白质中来测定胶原蛋白的合成。成纤维细胞的辐射诱导失活与终末分化纤维细胞的增加平行，表明过早的终末分化是放疗患者成纤维细胞对辐射的重要反应。存活的集落形成成纤维细胞显示出分化变化，与早期（E）分化状态相比，晚期（L）祖细胞成纤维细胞的L:E比率增加。此外，照射后观察到胶原蛋白产生增加。这些结果提供了证据，支持终末成纤维细胞分化在辐射诱导纤维化中的作用，并暗示放疗后存活的祖细胞群体可能比放疗前更容易发生终末分化。
