| Abstract |
Bone loss resulting from long-duration space flight is a well known
medical risk for space travellers, as a weakened skeleton is more
susceptible to bone fractures. In addition to weightlessness the astronaut
is also exposed to cosmic ionizing radiation. In order to elucidate
changes in bone cell metabolism by ionizing radiation, a ground-based bone
cell model has been developed. This model consists of a bunch of
immortalized murine osteocyte, osteoblast and pre-osteoblast cell lines
representing discrete stages of differentiation: The osteocyte cell line
MLO-Y4 (obtained from L. Bonewald, Kansas City, USA), the osteoblast cell
line OCT-1 (obtained from D. Chen, San Antonio, USA), and the subclones 4
and 24 of the osteoblast cell line MC3T3-E1 (obtained from ATCC, Manassas,
Virginia, USA). Regarding their growth properties, MLO-Y4 cells show the
highest growth velocity with a doubling time of 15.8 h. The osteoblast
cell line OCT-1 has a doubling time of 27.3 h. The respective values for
MC3T3-E1 subclone 24 and S4 are 90.5 h and 51.6 h. To investigate the
stage of differentiation, the expression of alkaline phosphatase, of
osteocalcin and of E11 was examined. Survival after X-ray exposure was
determined using the colony forming ability test. The resulting dose-
effect relationships revealed significant differences. The parameter D0 of
the survival curves ranges between 1.8 Gy for OCT-1, 1.9 Gy for MLO-Y4,
2.0 Gy for subclone 24 and 2.3 Gy for subclone 4. The quantitative
acquisition of DNA-strand breaks was performed by Fluorescent Analysis of
DNA-Unwinding (FADU). The results can be correlated with the corresponding
survival curve. In conclusion, the cell lines with higher differentiation
levels are less sensitive to radiation when compared to the lower
differentiated osteoblast cell lines.
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