Changes of fibrosis-related parameters after high- and low-LET irradiation of fibroblasts

Abstract

Purpose : To investigate the radiation-induced, premature terminal differentiation and collagen production of fibroblasts after heavy ion irradiation. These endpoints are discussed as an underlying cellular mechanism of fibrosis. Materials and methods : Normal human foreskin fibroblasts (AG1522B) were used to determine clonogenic survival, the premature differentiation and synthesis of extracellular matrix (ECM) proteins, e.g. collagen after irradiation with X-rays, 195 and 11.0 MeV u -1 carbon ions and 9.9 MeV u -1 nickel ions. Additionally, biopsies from the skin of minipigs were taken. Similar experiments were carried out after irradiation with X-rays and 195 MeV u -1 carbon ions. Results and conclusions : RBE for clonogenic survival as well as for fibrosis-related parameters for high-energy carbon ions are slightly above unity. Low-energy carbon ions with a higher LET are more efficient than X-rays, whereas the RBE of nickel ions is below unity. The results obtained for the differentiation pattern and protein production of porcine fibroblasts after irradiation with X-rays and high-energy carbon ions are in agreement with those obtained with human fibroblasts. An accumulation of fibrocytes with a concomitant increase in ECM protein production could be seen after in vitro irradiation. There is no indication of a higher RBE for fibrosis-related parameters compared with other endpoints (survival, chromosomal and DNA damage). The dose- and LET-dependence suggest that premature differentiation is a survival strategy after radiation damage.