Journal Article

Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after Radiation Exposure

Abend, Michael, Valente, Marco, Port, Matthias, Majewski, Matthäus, Hérodin, Francis, Drouet, Michel, Ullmann, Reinhard

2017

Overview

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.

• Publisher: MDPI
• Subject: Acute Radiation Syndrome - genetics / Animals / Disease Models, Animal / Gene Expression - radiation effects / Gene Expression Profiling / Gene Expression Regulation - radiation effects / Humans / MicroRNAs - genetics / Pancytopenia - etiology / Papio / Radiation Tolerance / RNA, Messenger - genetics