Radiat Environ Biophys (2007) 46:161–165 DOI 10.1007/s00411-006-0089-5 123 PROCEEDINGS OF THE 4TH IWSRR Protective eVects of L-selenomethionine on space radiation induced changes in gene expression J. Stewart · Y.-H. Ko · A. R. Kennedy Received: 20 September 2006 / Accepted: 20 December 2006 / Published online: 31 January 2007  Springer-Verlag 2007 Abstract Ionizing radiation can produce adverse bio- logical eVects in astronauts during space travel. Of par- ticular concern are the types of radiation from highly energetic, heavy, charged particles known as HZE par- ticles. The aims of our studies are to characterize HZE particle radiation induced biological eVects and evalu- ate the eVects of L-selenomethionine (SeM) on these adverse biological eVects. In this study, microarray technology was used to measure HZE radiation induced changes in gene expression, as well as to evalu- ate modulation of these changes by SeM. Human thy- roid epithelial cells (HTori-3) were irradiated (1 GeV/ n iron ions) in the presence or in the absence of 5 M SeM. At 6 h post-irradiation, all cells were harvested for RNA isolation. Gene Chip U133Av2 from AVyme- trix was used for the analysis of gene expression, and ANOVA and EASE were used for a determination of the genes and biological processes whose diVerential expression is statistically signiWcant. Results of this microarray study indicate that exposure to small doses of radiation from HZE particles, 10 and 20 cGy from iron ions, induces statistically signiWcant diVerential expression of 196 and 610 genes, respectively. In the presence of SeM, diVerential expression of 77 out of 196 genes (exposure to 10 cGy) and 336 out of 610 genes (exposure to 20 cGy) is abolished. In the pres- ence or in the absence of SeM, radiation from HZE particles induces diVerential expression of genes whose products have roles in the induction of G1/S arrest dur- ing the mitotic cell cycle, as well as heat shock proteins. Some of the genes, whose expressions were aVected by radiation from HZE particles and were unchanged in irradiated cells treated with SeM, have been shown to have altered expression levels in cancer cells. The con- clusions of this report are that radiation from HZE particles can induce diVerential expression of many genes, some of which are known to play roles in the same processes that have been shown to be activated in cells exposed to radiation from photons (like cell cycle arrest in G1/S), and that supplementation with SeM abolishes HZE particle-induced diVerential expression of many genes. Understanding the roles that these genes play in the radiation-induced transformation of cells may help to decipher the origins of radiation- induced cancer. Introduction Selenium is a known cancer preventive agent in experi- mental systems [1]. Activities of known selenoproteins are saturated in animals at a low dietary selenium level (0.1–0.4 ppm). A higherdietary concentration, 2 to 4 ppm, is required for a maximum cancer chemopreven- tive eVect. Selenomethionine (SeM) is the form of sele- nium currently being utilized by the National Cancer Institute in large-scale human cancer prevention trials, and is the form utilized in this study [3]. The mechanism(s) for the cancer preventive activity of selenium is unknown. There are many postulated mechanisms of action for selenium compounds as can- cer preventive agents, including the hypothesis that the cancer preventive activity of selenium is due to its J. Stewart · Y.-H. Ko · A. R. Kennedy (&) Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6072, USA e-mail: akennedy@mail.med.upenn.edu