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EC FP7, GA 295513 Biomarkers ranking Dicentric assay: DCA Translocation analysis : FISH Assay Micronucleus Assay : MN Laurence Roy 1 , Liz Ainsbury 2 , Christophe Badie 2 , Leonardo Barrios 3 , Céline Bassinet 1 , Paola Fattibene 4 , Eric Gregoire 1 , Ursula Oestreicher 5 , Gabriel Pantelias 6 , Sisko Salomaa 7 , Georgia Terzoudi 6 , Francois Trompier 1 , Anne Vral 8 , Andrzej Wojcik 9 , Ulrike Kulka 5 1 Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France 2 Public Health England, CRCE, Chilton, Didcot, Oxon, United Kingdom 3 Universitat Autonoma de Barcelona, Barcelona, Spain 4 Istituto di Superiore di Sanità, Rome, Italy 5 Bundesamt fuer Strahlenschutz, Department Radiation Protection and Health, Oberschleissheim, Germany 6 National Centre for Scientific Research "Demokritos", Athens, Greece 7 University of Eastern Finland, Kuopio, Finland 8 Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium 9 Stockholm University, Institute Molecular Biosciences, Stockholm, Sweden The harmonization process from the RENEB operational biological and physical retrospective dosimetry network to new biomarker validation. www.reneb.eu Background European Network for fast individual dose estimation in large scale scenarios EU project: 1.1.2012 – 31.12.2015 Established network: since 01.01.2016 Sensitivity Specificity Reporting time and capacity Time persistance L1 L2 L3 L4 L5 L6 L5 L7 L8 L9 L10 L11 L12 L13 L14 L15 Training Scientific visits Interlaboratory comparisons (ILC) Quality manual, documentation On going activities: - DCA: ILC on 500 cells in collaboration with EURADOS - FISH : homogenity in the scoring process - MN: improuvent of the staining Newly investigated 1 2 3 4 5 6 7 Gene expression assay Telomere Centromere γ-H2AX foci analysis RAMAN spectroscopy 2 institutions trained 9 institutions trained OSL: 5 institutions trained No training No training No training OSL: several ILC. Electronic components: Difficulties to identify the relevant components EPR: variability of material response Perform a standard ILC analysis and identify the parameters affecting the results Image and slides sharing. Z test passed successfully for several set of samples ILC on blood samples shipment not yet performed Some good candidates have been successfully used in ILC Effect of transportation conditions tested To be validated on in vivo exposed populations Involved in a large ILC Just one lab performing the assay up to now Two doses out of 4 have been correctly estimated Identification of the parameters affecting the results New ILC with more labs involved ILC carried out by dicentric scoring on images. Homogeneous results. Promising approach for highly accurate biodosimetry” ILC on slides and blood samples to be performed. Standard Z test to be used Abend et al. Radiation Research 2016, Ainsbury et al. IJRB 2016, Grégoire et al. IJRB 2016, Manning et al. IJRB 2016, Rothkamm et al. Radiation Research 2013, Terzoudi et al. IJRB 2016, CHO PCC Assay“ MAD: not as good as other biomarkers Has been successfully used in case of simulated partial body exposure Antibody validation process to be implemented in routine Glass: EPR and TL Electronic compo- nents: OSL and TL References Operational biomarkers Under validation L1 L2 L3 L4 L5 L6 L5 L7 L8 L9 L10 L11 L12 L13 L14 L15 Gene expression g-H2AX Dicentrics Micronuclei PCC Dicentrics OSL/TL OSL/TL g-H2AX PCC OSL/TL Dicentrics Raman Under investigation: Translocations

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Page 1: The harmonization process from the RENEB … · Abend et al. Radiation Research 2016, Ainsbury et al. IJRB 2016, Grégoire et al. IJRB 2016, Manning et al. IJRB 2016, Rothkamm et

EC FP7, GA 295513

Biomarkers ranking

Dicentricassay: DCA

Translocationanalysis :

FISH Assay

MicronucleusAssay : MN

Laurence Roy1, Liz Ainsbury2, Christophe Badie2, Leonardo Barrios3, Céline Bassinet1, Paola Fattibene4,

Eric Gregoire1, Ursula Oestreicher5, Gabriel Pantelias6, Sisko Salomaa7, Georgia Terzoudi6, Francois Trompier1,

Anne Vral8, Andrzej Wojcik9, Ulrike Kulka5

1 Institut de Radioprotection et de Sûreté Nucléaire, Fontenay-aux-Roses, France

2 Public Health England, CRCE, Chilton, Didcot, Oxon, United Kingdom

3 Universitat Autonoma de Barcelona, Barcelona, Spain

4 Istituto di Superiore di Sanità, Rome, Italy

5 Bundesamt fuer Strahlenschutz, Department Radiation Protection and Health, Oberschleissheim, Germany

6 National Centre for Scientific Research "Demokritos", Athens, Greece

7 University of Eastern Finland, Kuopio, Finland

8 Faculty of Medicine and Health Sciences, Ghent University, Gent, Belgium9 Stockholm University, Institute Molecular Biosciences, Stockholm, Sweden

The harmonization process from the RENEB

operational biological and physical

retrospective dosimetry network

to new biomarker validation.

www.reneb.eu

Background European Network for fast individual dose estimationin large scale scenarios

EU project: 1.1.2012 – 31.12.2015Established network: since 01.01.2016

Sensitivity Specificity Reporting time

and capacityTime

persistance

L1

L2

L3

L4

L5

L6

L5

L7

L8

L9L10

L11

L12

L13

L14

L15

Training Scientific visits Interlaboratory comparisons (ILC) Quality manual, documentation On going activities:

- DCA: ILC on 500 cells in collaboration with EURADOS- FISH : homogenity in the scoring process- MN: improuvent of the staining

Newly investigated

1 2 3 4 5 6 7Gene expression assay Telomere Centromereγ-H2AX foci analysis RAMAN spectroscopy

2 institutions trained

9 institutions trained

OSL: 5institutions trained

No training No training No training

OSL: several ILC. Electronic components: Difficulties to identify the relevant componentsEPR: variability of material response

Perform a standard ILC analysis and identify the parameters affecting the results

Image and slides sharing.Z test passed successfully for several set of samples

ILC on blood samples shipment not yet performed

Some good candidates have been successfully used in ILCEffect of transportation conditions tested

To be validated on in vivo exposed populations

Involved in a large ILCJust one lab performing the assay up to nowTwo doses out of 4 have been correctly estimated

Identification of the parameters affecting the resultsNew ILC with more labs involved

ILC carried out by dicentricscoring on images. Homogeneous results. Promising approach for highly accurate biodosimetry”

ILC on slides and blood samples to be performed.Standard Z test to be used

Abend et al. Radiation Research 2016, Ainsbury et al. IJRB 2016, Grégoire et al. IJRB 2016, Manning et al. IJRB 2016, Rothkamm et al. Radiation Research 2013, Terzoudi et al. IJRB 2016,

CHO PCC Assay“

MAD: not as good as other biomarkersHas been successfully used in case of simulated partial body exposure

Antibody validation process to be implemented in routine

Glass:EPRand TL

Electronic compo-nents: OSL and TL

References

Operational biomarkers

Under validation

L1

L2

L3L4

L5

L6

L5

L7

L8

L9L10

L11

L12

L13

L14

L15

Gene expression

g-H2AX

DicentricsMicronuclei

PCC

Dicentrics

OSL/TL

OSL/TL

g-H2AX PCCOSL/TL Dicentrics Raman

Under

investigation:Translocations

http://www.reneb.eu/

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