PMID- 29474504
OWN - NLM
STAT- MEDLINE
DCOM- 20180612
LR  - 20181113
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 13
IP  - 2
DP  - 2018
TI  - The first in vivo multiparametric comparison of different radiation exposure
      biomarkers in human blood.
PG  - e0193412
LID - 10.1371/journal.pone.0193412 [doi]
AB  - The increasing risk of acute large-scale radiological/nuclear exposures of
      population underlines the necessity of developing new, rapid and high throughput 
      biodosimetric tools for estimation of received dose and initial triage. We aimed 
      to compare the induction and persistence of different radiation exposure
      biomarkers in human peripheral blood in vivo. Blood samples of patients with
      indicated radiotherapy (RT) undergoing partial body irradiation (PBI) were
      obtained soon before the first treatment and then after 24 h, 48 h, and 5 weeks; 
      i.e. after 1, 2, and 25 fractionated RT procedures. We collected circulating
      peripheral blood from ten patients with tumor of endometrium (1.8 Gy per
      fraction) and eight patients with tumor of head and neck (2.0-2.121 Gy per
      fraction). Incidence of dicentrics and micronuclei was monitored as well as
      determination of apoptosis and the transcription level of selected
      radiation-responsive genes. Since mitochondrial DNA (mtDNA) has been reported to 
      be a potential indicator of radiation damage in vitro, we also assessed mtDNA
      content and deletions by novel multiplex quantitative PCR. Cytogenetic data
      confirmed linear dose-dependent increase in dicentrics (p < 0.01) and micronuclei
      (p < 0.001) in peripheral blood mononuclear cells after PBI. Significant
      up-regulations of five previously identified transcriptional biomarkers of
      radiation exposure (PHPT1, CCNG1, CDKN1A, GADD45, and SESN1) were also found (p <
      0.01). No statistical change in mtDNA deletion levels was detected; however, our 
      data indicate that the total mtDNA content decreased with increasing number of RT
      fractions. Interestingly, the number of micronuclei appears to correlate with
      late radiation toxicity (r2 = 0.9025) in endometrial patients suggesting the
      possibility of predicting the severity of RT-related toxicity by monitoring this 
      parameter. Overall, these data represent, to our best knowledge, the first study 
      providing a multiparametric comparison of radiation biomarkers in human blood in 
      vivo, which have potential for improving biological dosimetry.
FAU - Tichy, Ales
AU  - Tichy A
AUID- ORCID: 0000-0002-8262-5703
AD  - Department of Radiobiology, Faculty of Military Health Sciences, Hradec Kralove, 
      University of Defence in Brno, Hradec Kralove, Czech Republic.
AD  - Biomedical Research Centre, University Hospital, Hradec Kralove, Czech Republic.
FAU - Kabacik, Sylwia
AU  - Kabacik S
AD  - Cancer Mechanisms and Biomarkers group, Radiation Effects Department, Centre for 
      Radiation, Chemical and Environmental Hazards, Public Health of England, Didcot, 
      United Kingdom.
FAU - O'Brien, Grainne
AU  - O'Brien G
AD  - Cancer Mechanisms and Biomarkers group, Radiation Effects Department, Centre for 
      Radiation, Chemical and Environmental Hazards, Public Health of England, Didcot, 
      United Kingdom.
FAU - Pejchal, Jaroslav
AU  - Pejchal J
AD  - Department of Toxicology, Faculty of Military Health Sciences, Hradec Kralove,
      University of Defence in Brno, Czech Republic.
FAU - Sinkorova, Zuzana
AU  - Sinkorova Z
AD  - Department of Radiobiology, Faculty of Military Health Sciences, Hradec Kralove, 
      University of Defence in Brno, Hradec Kralove, Czech Republic.
FAU - Kmochova, Adela
AU  - Kmochova A
AD  - Department of Radiobiology, Faculty of Military Health Sciences, Hradec Kralove, 
      University of Defence in Brno, Hradec Kralove, Czech Republic.
FAU - Sirak, Igor
AU  - Sirak I
AD  - Department of Oncology and Radiotherapy and 4th Department of Internal Medicine -
      Hematology, University Hospital, Hradec Kralove, Czech Republic.
FAU - Malkova, Andrea
AU  - Malkova A
AD  - Department of Hygiene and Preventive Medicine, Faculty of Medicine in Hradec
      Kralove, Charles University in Prague, Hradec Kralove, Czech Republic.
FAU - Beltran, Caterina Gomila
AU  - Beltran CG
AD  - Institute for Global Health, Barcelona, Spain.
FAU - Gonzalez, Juan Ramon
AU  - Gonzalez JR
AD  - Institute for Global Health, Barcelona, Spain.
FAU - Grepl, Jakub
AU  - Grepl J
AD  - Department of Radiobiology, Faculty of Military Health Sciences, Hradec Kralove, 
      University of Defence in Brno, Hradec Kralove, Czech Republic.
AD  - Department of Oncology and Radiotherapy and 4th Department of Internal Medicine -
      Hematology, University Hospital, Hradec Kralove, Czech Republic.
FAU - Majewski, Matthaeus
AU  - Majewski M
AD  - Bundeswehr Institute of Radiobiology, Munich, Germany.
FAU - Ainsbury, Elizabeth
AU  - Ainsbury E
AD  - Cancer Mechanisms and Biomarkers group, Radiation Effects Department, Centre for 
      Radiation, Chemical and Environmental Hazards, Public Health of England, Didcot, 
      United Kingdom.
FAU - Zarybnicka, Lenka
AU  - Zarybnicka L
AD  - Department of Radiobiology, Faculty of Military Health Sciences, Hradec Kralove, 
      University of Defence in Brno, Hradec Kralove, Czech Republic.
FAU - Vachelova, Jana
AU  - Vachelova J
AD  - Department of Radiation Dosimetry, Nuclear Physics Institute of the Czech Academy
      of Sciences, Prague, Czech Republic.
FAU - Zavrelova, Alzbeta
AU  - Zavrelova A
AD  - Department of Oncology and Radiotherapy and 4th Department of Internal Medicine -
      Hematology, University Hospital, Hradec Kralove, Czech Republic.
FAU - Davidkova, Marie
AU  - Davidkova M
AD  - Department of Radiation Dosimetry, Nuclear Physics Institute of the Czech Academy
      of Sciences, Prague, Czech Republic.
FAU - Markova Stastna, Marketa
AU  - Markova Stastna M
AD  - Institute for Hematology and Blood Transfusion, Hospital Na Bulovce, Prague,
      Czech Republic.
FAU - Abend, Michael
AU  - Abend M
AD  - Bundeswehr Institute of Radiobiology, Munich, Germany.
FAU - Pernot, Eileen
AU  - Pernot E
AD  - Institute for Global Health, Barcelona, Spain.
FAU - Cardis, Elisabeth
AU  - Cardis E
AD  - Institute for Global Health, Barcelona, Spain.
FAU - Badie, Christophe
AU  - Badie C
AD  - Cancer Mechanisms and Biomarkers group, Radiation Effects Department, Centre for 
      Radiation, Chemical and Environmental Hazards, Public Health of England, Didcot, 
      United Kingdom.
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180223
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Biomarkers)
RN  - 0 (DNA, Mitochondrial)
SB  - IM
MH  - Aged
MH  - Aged, 80 and over
MH  - Biomarkers/blood
MH  - Chromosome Aberrations
MH  - DNA, Mitochondrial/radiation effects
MH  - Dose-Response Relationship, Radiation
MH  - Endometrial Neoplasms/blood/radiotherapy
MH  - Female
MH  - Head and Neck Neoplasms/blood/radiotherapy
MH  - Humans
MH  - Leukocytes/pathology/*radiation effects
MH  - Male
MH  - Micronuclei, Chromosome-Defective
MH  - Middle Aged
MH  - *Radiation Exposure
MH  - Radiometry/*methods
MH  - Radiotherapy/adverse effects
MH  - Radiotherapy Dosage
MH  - Transcription, Genetic/radiation effects
PMC - PMC5825084
EDAT- 2018/02/24 06:00
MHDA- 2018/06/13 06:00
CRDT- 2018/02/24 06:00
PHST- 2017/11/10 00:00 [received]
PHST- 2018/02/10 00:00 [accepted]
PHST- 2018/02/24 06:00 [entrez]
PHST- 2018/02/24 06:00 [pubmed]
PHST- 2018/06/13 06:00 [medline]
AID - 10.1371/journal.pone.0193412 [doi]
AID - PONE-D-17-39917 [pii]
PST - epublish
SO  - PLoS One. 2018 Feb 23;13(2):e0193412. doi: 10.1371/journal.pone.0193412.
      eCollection 2018.