ORIGINAL PAPER Cell cycle delay in murine pre-osteoblasts is more pronounced after exposure to high-LET compared to low-LET radiation Yueyuan Hu • Christine E. Hellweg • Christa Baumstark-Khan • Gu ¨ nther Reitz • Patrick Lau Received: 7 May 2013 / Accepted: 5 November 2013 / Published online: 16 November 2013 Ó Springer-Verlag Berlin Heidelberg 2013 Abstract 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 dis- turbs 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 radia- tion, 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/lm 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 regu- lated through elevated CDKN1A expression. Keywords Ionizing radiation Á RBE Á Osteoblastic cells Á DNA damage Á Cell cycle Á Transcription factors Á Gene expression Introduction Space radiation contains high-energy high Z (HZE) heavy charged particles, an important component of space radi- ation contributing strongly to risks of human spaceflight (Cucinotta and Durante 2006). High-energy galactic cos- mic rays and solar particle events exert distinct biological damage compared to radiation on Earth, making it difficult to predict health risks to astronauts (Schimmerling 1992; Reitz et al. 2009; Kronenberg and Cucinotta 2012). In addition to the effects of radiation, bone loss is a serious problem for astronauts traveling in space. Previous studies have demonstrated that astronauts on 4–6-month missions aboard the International Space Station experience 0.9–1.6 % femoral and vertebral bone loss per month (Lang et al. 2004). Significant decreases in bone strength due to loss of bone mass or architectural stability can affect mission success because they increase the risk of serious fractures (Willey et al. 2011). It is less clear if the com- bination of radiation exposure and microgravity has syn- ergistic effects on osteoblast function (Bandstra et al. 2008). Previous in vivo studies performed in mouse models clearly demonstrated prolonged and profound losses of trabecular and/or cortical bone following exposure to acute radiation doses (Hamilton et al. 2006; Lloyd et al. 2008). In addition, radiation therapy for cancer is associated with immediate and long-term damage to soft tissue and bone (Rana et al. 2012). Bone is a dynamic tissue that constantly undergoes modeling and remodeling via osteo- clastic bone resorption and osteoblastic bone formation to Y. Hu Á C. E. Hellweg Á C. Baumstark-Khan Á G. Reitz Á P. Lau (&) Division of Radiation Biology, Institute of Aerospace Medicine, German Aerospace Center (DLR), Linder Hoehe, 51147 Cologne, Germany e-mail: patrick.lau@dlr.de 123 Radiat Environ Biophys (2014) 53:73–81 DOI 10.1007/s00411-013-0499-0