Radiation-induced alterations of the proliferation dynamics of human skin fibroblasts after repeated irradiation in the subtherapeutic dose range

Abstract

Purpose: The aim of this study was to determine the effect of single and multiple irradiations on the differentiation and proliferation pattern of the stem cell system of human fibroblasts.

Methods: The pattern of differentiation of fibroblast cultures was analyzed by morphological criteria using colony forming assays. Proliferation rates were assessed by cell counting and measuring the incorporation of BrdU.

Results: Ionizing radiation both in low and high dose ranges exerts differential effects on the cellular processes of differentiation and proliferation in human fibroblasts. Single irradiations of fibroblasts in the dose range of 1 to 8 Gy induced terminal differentiation into postmitotic fibrocytes at high percentage level. Irradiation of long-term cultures of fibroblasts with repeated doses of 0.2, 0.6 and 1.0 Gy revealed that only in cultures, which were irradiated repeatedly (x 10) with 0.6 and 1.0 Gy a marked reduction of the proliferation capacity was apparent. Inhibition of proliferation by repeated irradiations with cumulative doses up to 10 Gy was not more pronounced as compared to single irradiations.

Conclusion: 1. These results of radiation-induced changes in the proliferation and differentiation pattern of cells may be a basis for the understanding of the cellular processes leading to radiation-induced fibrosis and tissue aging. 2. Multiple irradiations with single doses up to 1 Gy and cumulative doses up to 10 Gy did not change the radiosensitivity of fibroblast cultures regarding effects on cell proliferation.