title: Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after Radiation Exposure.
abstract: Radiosensitivity differs in humans and likely among primates. The reasons are not well known. We examined pre-exposure gene expression in baboons (n= 17) who developed haematologic acute radiation syndrome (HARS) without pancytopenia or a more aggravated HARS with pancytopenia after irradiation. We evaluated gene expression in a two stage study design where stage I comprised a whole genome screen for messenger RNAs (mRNA) (microarray) and detection of 667 microRNAs (miRNA) (real-time quantitative polymerase chain reaction (qRT-PCR) platform). Twenty candidate mRNAs and nine miRNAs were selected for validation in stage II (qRT-PCR). None of the mRNA species could be confirmed during the validation step, but six of the nine selected candidate miRNA remained significantly different during validation. In particular, miR-425-5p (receiver operating characteristic = 0.98;p= 0.0003) showed nearly complete discrimination between HARS groups with and without pancytopenia. Target gene searches of miR-425-5p identified new potential mRNAs and associated biological processes linked with radiosensitivity. We found that one miRNA species examined in pre-exposure blood samples was associated with HARS characterized by pancytopenia and identified new target mRNAs that might reflect differences in radiosensitivity of irradiated normal tissue.
authors.affiliation: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany. MatthiasPort@bundeswehr.org.
authors.forename: Matthias
authors.initials: M
authors.lastname: Port
authors.affiliation: Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France. francis.herodin@wanadoo.fr.
authors.forename: Francis
authors.initials: F
authors.lastname: Hérodin
authors.affiliation: Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France. marco.valente@live.fr.
authors.forename: Marco
authors.initials: M
authors.lastname: Valente
authors.affiliation: Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France. michel.drouet@irba.fr.
authors.forename: Michel
authors.initials: M
authors.lastname: Drouet
authors.affiliation: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany. reinhard1ullmann@bundeswehr.org.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Ullmann
authors.affiliation: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany. matthaeusmajewski@bundeswehr.org.
authors.forename: Matthäus
authors.initials: M
authors.lastname: Majewski
authors.affiliation: Bundeswehr Institute of Radiobiology, 80937 Munich, Germany. michaelabend@bundeswehr.org.
authors.forename: Michael
authors.initials: M
authors.lastname: Abend
mesh_terms: D054508:Acute Radiation Syndrome / Q000235:genetics*; D000818:Animals; D004195:Disease Models, Animal; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D010198:Pancytopenia / Q000209:etiology*; D010215:Papio; D012333:RNA, Messenger / Q000235:genetics*; D011836:Radiation Tolerance
chemical_list: D035683:MicroRNAs; D012333:RNA, Messenger
keywords: gene expression; haematologic acute radiation syndrome (HARS); miRNA; pancytopenia; radiosensitivity