Protective effects of <Emphasis Type="SmallCaps">l</Emphasis>-selenomethionine on space radiation induced changes in gene expression |
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Authors: | J Stewart Y -H Ko A R Kennedy |
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Institution: | (1) Department of Radiation Oncology, University of Pennsylvania School of Medicine, 195 John Morgan Building, 3620 Hamilton Walk, Philadelphia, PA 19104-6072, USA |
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Abstract: | Ionizing radiation can produce adverse biological effects in astronauts during space travel. Of particular concern are the
types of radiation from highly energetic, heavy, charged particles known as HZE particles. The aims of our studies are to
characterize HZE particle radiation induced biological effects and evaluate the effects of l-selenomethionine (SeM) on these adverse biological effects. In this study, microarray technology was used to measure HZE
radiation induced changes in gene expression, as well as to evaluate modulation of these changes by SeM. Human thyroid epithelial
cells (HTori-3) were irradiated (1 GeV/n iron ions) in the presence or in the absence of 5 μM SeM. At 6 h post-irradiation,
all cells were harvested for RNA isolation. Gene Chip U133Av2 from Affymetrix was used for the analysis of gene expression,
and ANOVA and EASE were used for a determination of the genes and biological processes whose differential expression is statistically
significant. 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 significant differential expression of 196 and 610 genes, respectively. In the
presence of SeM, differential 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 presence or in the absence of SeM, radiation from HZE particles induces differential expression
of genes whose products have roles in the induction of G1/S arrest during the mitotic cell cycle, as well as heat shock proteins.
Some of the genes, whose expressions were affected 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 conclusions of this report are that
radiation from HZE particles can induce differential 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 differential 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. |
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