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The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

ABSTRACT: 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.

SUBMITTER: Tichy A

PROVIDER: S-EPMC5825084 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

Tichy Ales A Kabacik Sylwia S O'Brien Grainne G Pejchal Jaroslav J Sinkorova Zuzana Z Kmochova Adela A Sirak Igor I Malkova Andrea A Beltran Caterina Gomila CG Gonzalez Juan Ramon JR Grepl Jakub J Majewski Matthaeus M Ainsbury Elizabeth E Zarybnicka Lenka L Vachelova Jana J Zavrelova Alzbeta A Davidkova Marie M Markova Stastna Marketa M Abend Michael M Pernot Eileen E Cardis Elisabeth E Badie Christophe C

PloS one 20180223 2

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 treatme ...[more]

PMID: 29474504

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Project description:BackgroundMyocardial T1 and T2 mapping are reliable diagnostic markers for the detection and follow up of acute myocarditis. The aim of this study was to compare the diagnostic performance of current mapping measurement approaches to differentiate between myocarditis patients and healthy individuals.MethodsFifty patients with clinically defined acute myocarditis and 30 healthy controls underwent cardiovascular magnetic resonance (CMR). Myocardial T1 relaxation times, T2 relaxation times, left ventricular (LV) function, T2 ratio, early gadolinium enhancement ratio, and presence of late gadolinium enhancement (LGE) were analysed. Native T1 and T2 relaxation times, as well as extracellular volume fraction (ECV) were measured for the entire LV myocardium (global), within the midventricular short axis slice (mSAX), within the midventricular septal wall (ConSept), and within the remote myocardium (remote). Receiver operating characteristics analysis was performed to compare diagnostic performance.ResultsAll measurement approaches revealed significantly higher native T1 and T2 relaxation times as well as ECV values in patients compared to healthy controls (p < 0.05 for all parameters). The global measurement approach showed highest diagnostic performance regarding all mapping parameters (AUCs, native T1: 0.903, T2: 0.847, ECV: 0.731). Direct comparison of the different measurement approaches revealed significant differences in diagnostic performance between the global and the remote approach regarding T1 relaxation times and ECV (p = 0.001 and p = 0.002 respectively). Further, the global measurement approach revealed significantly higher T1 relaxation times compared to the ConSept approach (AUCs: 0.903 vs. 0.783; p = 0.003) and nearly significant differences compared to the mSAX approach (AUC: 0.850; p = 0.051). T2 relaxation times showed no significant differences between all measurement approaches (p > 0.050 for all parameters).ConclusionsNative T1 and T2 mapping allow for accurate detection of acute myocarditis irrespective of the measurement approach used. Even measurements performed exclusively within remote myocardium allow for reliable detection of acute myocarditis, demonstrating diffuse involvement of disease despite a mostly regional or patchy distribution pattern of visible pathologies. The global measurement approach provides the overall best diagnostic performance in acute myocarditis for both T1 and T2 mapping.

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The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

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The first in vivo multiparametric comparison of different radiation exposure biomarkers in human blood.

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