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.
Highlights
Understanding individual human responses to radiation exposure with respect to tissue damage or developing radiation-related sequelae would be of benefit in several instances
Predictive strategies to determine the radiosensitivity of patient tumours and normal tissue a priori would be essential for personalized cancer therapy [1]
Astronauts traveling to Mars in 2030 would benefit from knowing their individualized radiation-related risk profile [2]; in radiological or nuclear scenarios, individuals exposed to the same magnitude of radiation might develop different degrees of haematologic acute radiation syndrome (HARS) because of inter-individual differences in radiosensitivity [3]
Summary
Understanding individual human responses to radiation exposure with respect to tissue damage or developing radiation-related sequelae would be of benefit in several instances. Predictive strategies to determine the radiosensitivity of patient tumours and normal tissue a priori would be essential for personalized cancer therapy [1]. Astronauts traveling to Mars in 2030 would benefit from knowing their individualized radiation-related risk profile [2]; in radiological or nuclear scenarios, individuals exposed to the same magnitude of radiation might develop different degrees of haematologic acute radiation syndrome (HARS) because of inter-individual differences in radiosensitivity [3]. Identifying radiosensitive individuals would aid in avoiding misclassification of those persons with low vs high exposures. Haematologic acute radiation syndrome develops days or weeks after radiation exposure depending on the absorbed dose. Medical management decision making such as hospitalization or administration of granulocyte colony stimulating factor (G-CSF) would certainly benefit from an early diagnosis and prediction of the likely clinical course to help ensure a favourable outcome [4]
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