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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.
PMID
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Authors

Mayor MeshTerms

Gene Expression

Keywords

gene expression

haematologic acute radiation syndrome (HARS)

miRNA

pancytopenia

radiosensitivity

Journal Title international journal of molecular sciences
Publication Year Start




PMID- 28257102
OWN - NLM
STAT- MEDLINE
DA  - 20170303
DCOM- 20170317
LR  - 20170317
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 18
IP  - 3
DP  - 2017 Mar 02
TI  - Pre-Exposure Gene Expression in Baboons with and without Pancytopenia after
      Radiation Exposure.
LID - E541 [pii]
LID - 10.3390/ijms18030541 [doi]
AB  - 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.
FAU - Port, Matthias
AU  - Port M
AD  - Bundeswehr Institute of Radiobiology, 80937 Munich, Germany.
      [email protected]
FAU - Herodin, Francis
AU  - Herodin F
AD  - Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France.
      [email protected]
FAU - Valente, Marco
AU  - Valente M
AD  - Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France.
      [email protected]
FAU - Drouet, Michel
AU  - Drouet M
AD  - Institut de Recherche Biomedicale des Armees, 91220 Bretigny-sur-Orge, France.
      [email protected]
FAU - Ullmann, Reinhard
AU  - Ullmann R
AD  - Bundeswehr Institute of Radiobiology, 80937 Munich, Germany.
      [email protected]
FAU - Majewski, Matthaus
AU  - Majewski M
AD  - Bundeswehr Institute of Radiobiology, 80937 Munich, Germany.
      [email protected]
FAU - Abend, Michael
AU  - Abend M
AD  - Bundeswehr Institute of Radiobiology, 80937 Munich, Germany.
      [email protected]
LA  - eng
PT  - Journal Article
DEP - 20170302
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Acute Radiation Syndrome/*genetics
MH  - Animals
MH  - Disease Models, Animal
MH  - *Gene Expression/radiation effects
MH  - Gene Expression Profiling
MH  - Gene Expression Regulation/radiation effects
MH  - Humans
MH  - MicroRNAs/*genetics
MH  - Pancytopenia/*etiology
MH  - Papio
MH  - RNA, Messenger/*genetics
MH  - Radiation Tolerance
OTO - NOTNLM
OT  - gene expression
OT  - haematologic acute radiation syndrome (HARS)
OT  - miRNA
OT  - pancytopenia
OT  - radiosensitivity
EDAT- 2017/03/04 06:00
MHDA- 2017/03/18 06:00
CRDT- 2017/03/04 06:00
PHST- 2017/01/27 [received]
PHST- 2017/02/17 [revised]
PHST- 2017/02/24 [accepted]
AID - ijms18030541 [pii]
AID - 10.3390/ijms18030541 [doi]
PST - epublish
SO  - Int J Mol Sci. 2017 Mar 2;18(3). pii: E541. doi: 10.3390/ijms18030541.

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