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


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.


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.
Fournier
C
C
GSI/Biophysics, Planckstrasse 1, D-64291 Darmstadt, Germany. c.fournier@gsi.de
Scholz
M
M
Weyrather
W K
WK
Rodemann
H P
HP
Kraft
G
G
D000818:Animals; D002454:Cell Differentiation / Q000528:radiation effects; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D003094:Collagen / Q000096:biosynthesis; D003114:Colony-Forming Units Assay; D016326:Extracellular Matrix Proteins / Q000096:biosynthesis; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects*; D005355:Fibrosis; D006801:Humans; D066298:In Vitro Techniques; D018499:Linear Energy Transfer; D012062:Relative Biological Effectiveness; D013552:Swine; D013556:Swine, Miniature
D016326:Extracellular Matrix Proteins; D003094:Collagen