Cell cycle delay in murine pre-osteoblasts is more pronounced after exposure to high-LET compared to low-LET radiation.
Space radiation contains a complex mixture of particles comprised primarily of protons and high-energy heavy ions. Radiation risk is considered one of the major health risks for astronauts who embark on both orbital and interplanetary space missions. Ionizing radiation dose-dependently kills cells, damages genetic material, and disturbs cell differentiation and function. The immediate response to ionizing radiation-induced DNA damage is stimulation of DNA repair machinery and activation of cell cycle regulatory checkpoints. To date, little is known about cell cycle regulation after exposure to space-relevant radiation, especially regarding bone-forming osteoblasts. Here, we assessed cell cycle regulation in the osteoblastic cell line OCT-1 after exposure to various types of space-relevant radiation. The relative biological effectiveness (RBE) of ionizing radiation was investigated regarding the biological endpoint of cellular survival ability. Cell cycle progression was examined following radiation exposure resulting in different RBE values calculated for a cellular survival level of 1 %. Our findings indicate that radiation with a linear energy transfer (LET) of 150 keV/μm was most effective in inducing reproductive cell killing by causing cell cycle arrest. Expression analyses indicated that cells exposed to ionizing radiation exhibited significantly up-regulated p21(CDKN1A) gene expression. In conclusion, our findings suggest that cell cycle regulation is more sensitive to high-LET radiation than cell survival, which is not solely regulated through elevated CDKN1A expression.
Division of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147, Cologne, Germany.
Yueyuan
Y
Hu
Christine E
CE
Hellweg
Christa
C
Baumstark-Khan
Günther
G
Reitz
Patrick
P
Lau
D000818:Animals; D002453:Cell Cycle / Q000528:radiation effects*; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D005118:Extraterrestrial Environment; D005786:Gene Expression Regulation / Q000528:radiation effects; D020450:Heavy Ions / Q000009:adverse effects; D018499:Linear Energy Transfer; D051379:Mice; D010006:Osteoblasts / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects; D012062:Relative Biological Effectiveness
D050759:Cyclin-Dependent Kinase Inhibitor p21