Vali lidating Geant4-DNA for DNA Double Strand Brakes (DSB): A - - PowerPoint PPT Presentation

Vali lidating Geant4-DNA for DNA Double Strand Brakes (DSB): A preliminary ry study

Konstantinos Chatzipapas1, Panagiotis Papadimitroulas2, Mohammad Ali Obeidat3, Neil Kirby3, George Loudos4, Niko Papanikolaou3 and George C. Kagadis1

(1) University of Patras, Department of Medical Physics, Patras, Greece (2) BET Solutions, R&D Department, Athens, Greece (3) University of Texas, Health Science Center, San Antonio, USA (4) Athens University of Applied Sciences, Athens, Greece

Outline

• Introduction
• DNA-DSB Dosimeter
• DNA-DSB Algorithm
• Results
• Discussion

MCMA 2017, Napoli

Introduction (1/2)

• Geant4-DNA:
• is a common platform available to all (Villagrasa et al, 2011)
• can simulate free radical (Karamitros et al, 2014)
• can simulate DNA irradiation and count SSB and DSB (Delage et al, 2015)
• can accumulate complex DNA models created by DnaFabric (Meylan et al, 2017)
• needs validation studies for evaluation of its accuracy (Incerti et al, 2016)
• Prediction of biological consequences

MCMA 2017, Napoli

Introduction (2/2)

• Measuring DNA DSB for dosimetry
• Gel Electrophoresis
• W. Chen, E. Blazek, and I. Rosenberg. "The relaxation of supercoiled DNA molecules as a biophysical

dosimeter for ionizing radiations: a feasibility study." Medical Physics 22.9 (1995): 1369-1375.

• Precision was just 5%
• Not simple or fast

MCMA 2017, Napoli

DNA-DSB Dosimeter (1/2)

• Measures directly the biological effect.
• M.Obeidat,K.Cline,S.Stathakis,N.Papanikolaou,K.Rasmussen,A.Gutierrez,CS.Ha,SE.Lee,EY.Shim,N.Kirby, “MO-AB-BRA-

04: Radiation Measurements with a DNA Double-Strand-Break Dosimeter”, in Medical Physics 43(6), June 2016

• M.Obeidat,K.Cline,S.Stathakis,N.Papanikolaou,K.Rasmussen,A.Gutierrez,CS.Ha,SE.Lee,EY.Shim,N.Kirby,

“TH-CD-201- 11: Optimizing the Response and Cost of a DNA Double-Strand-Brake Dosimeter”, in Medical Physics 43(6), June 2016

MCMA 2017, Napoli

DNA-DSB Dosimeter (2/2)

• Taking advantage of the magnetic properties of Streptavidin.
• User-friendly
• Accurate

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DNA-DSB Calculation Algorithm

• Simulation of direct damage on the DNA molecule
• PDB4DNA example
• Dinucleosome as the DNA molecule
• Radiation by an 6MV Varian Linac (Ankit, 2016)
• The class that calculates SSB and DSB needed

modification, because:

• Overestimation of SSB number
• Does not find every DSB

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DNA-DSB Calculation Algorithm

• The new class:
• checks every SSB if it is DSB
• Two main parameters can be defined

(as in the default example)

• With trial and error we defined:
• Energy threshold

( 9 eV )

• Distance threshold

( 2 bases )

While there is data for strand1, check if E ≥ Et on base While there is data for strand2, check if E ≥ Et on base Check if D ≤ Dt SSB1 = SSB1 +1 Erase processed data While there is data for strand2, check if E≥Et on base SSB1 = SSB1 +1 SSB2 = SSB2 +1 Erase processed data DSB = DSB +1 Erase processed data SSB2 = SSB2 +1 Erase processed data true true true false false true false false

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Results (1/2)

• Diagram presenting the probability of DSB depending on Dose.

10 20 30 40 50 60 70 80 90 100 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160

Probability of DSB (%) Dose (Gy)

Comparison of DSB probability vs. the absorbed dose

Experimental data using DNA dosimeter G4-DNA using proposed algorithm and E(thres)=9, D(thres)=2 G4-DNA using default algorithm and E(thres)=9, D(thres)=2 G4-DNA using proposed algorithm and E(thres)=17.5, D(thres)=10 G4-DNA using default algorithm and E(thres)=17.5, D(thres)=10

MCMA 2017, Napoli

Results (2/2)

• We compare the output of both algorithms (default- proposed) with

experimental data using the DNA dosimeter.

0% 20% 40% 60% 80% 100% 120% 140% 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160

Statistical Difference Dose (Gy)

Statistical Difference of Experimental Data with G4-DNA

G4-DNA using proposed algorithm and E(thres)=9, D(thres)=2 G4-DNA using default algorithm and E(thres)=9, D(thres)=2 G4-DNA using proposed algorithm and E(thres)=17.5, D(thres)=10 G4-DNA using default algorithm and E(thres)=17.5, D(thres)=10

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Discussion

• Experimental data for quantifying DNA-DSB were used for validation

study of Geant4-DNA code

• The proposed algorithm for the calculation of DNA-DSB provides

results with enough accuracy and the difference ranging from 8%-25%

• The proposed study need to be extended to more DNA molecules and

to a variety of irradiations (keV-MeV)

• More experimental data are needed for better evaluation
• Chemical interactions need to be considered for more accurate

simulations

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This study is part of a project that has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Skłodowska-Curie grant agreement No 691203.

Acknowledgments

MCMA 2017, Napoli

Vali lidating Geant4-DNA for DNA Double Strand Brakes (DSB): A preliminary ry study

Konstantinos Chatzipapas1, Panagiotis Papadimitroulas2, Mohammad Ali Obeidat3, Neil Kirby3, George Loudos4, Niko Papanikolaou3 and George C. Kagadis1

(1) University of Patras, Department of Medical Physics, Patras, Greece (2) BET Solutions, R&D Department, Athens, Greece (3) University of Texas, Health Science Center, San Antonio, USA (4) Athens University of Applied Sciences, Athens, Greece

Thank you for your attention