Vali lidating Geant4-DNA for DNA Double Strand Brakes (DSB): A preliminary ry study Konstantinos Chatzipapas 1 , Panagiotis Papadimitroulas 2 , Mohammad Ali Obeidat 3 , Neil Kirby 3 , George Loudos 4 , Niko Papanikolaou 3 and George C. Kagadis 1 (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 MCMA 2017, Napoli
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 MCMA 2017, Napoli
DNA-DSB Calculation Algorithm While there is data for strand1, check if E ≥ Et on base false true While there is data • The new class: for strand2, check if E ≥ Et on base • checks every SSB if it is DSB true false • Two main parameters can be defined SSB1 = SSB1 +1 Check if D ≤ Dt Erase processed data (as in the default example) true false • With trial and error we defined: SSB1 = SSB1 +1 DSB = DSB +1 • Energy threshold ( 9 eV ) SSB2 = SSB2 +1 Erase processed data Erase processed data • Distance threshold ( 2 bases ) While there is data for strand2, check if E≥Et on base false true SSB2 = SSB2 +1 Erase processed data MCMA 2017, Napoli
Results (1/2) • Diagram presenting the probability of DSB depending on Dose. Comparison of DSB probability vs. the absorbed dose Probability of DSB (%) 100 Experimental data using DNA dosimeter G4-DNA using proposed algorithm and E(thres)=9, D(thres)=2 90 G4-DNA using default algorithm and E(thres)=9, D(thres)=2 80 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 70 60 50 40 30 20 10 Dose (Gy) 0 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 MCMA 2017, Napoli
Results (2/2) • We compare the output of both algorithms (default- proposed) with experimental data using the DNA dosimeter. Statistical Difference of Experimental Data with G4-DNA Statistical Difference 140% G4-DNA using proposed algorithm and E(thres)=9, D(thres)=2 G4-DNA using default algorithm and E(thres)=9, D(thres)=2 120% 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)=10 100% 80% 60% 40% 20% Dose (Gy) 0% 0 10 20 30 40 50 60 70 80 90 100 110 120 130 140 150 160 MCMA 2017, Napoli
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 MCMA 2017, Napoli
Acknowledgments 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. MCMA 2017, Napoli
Vali lidating Geant4-DNA for DNA Double Strand Brakes (DSB): A preliminary ry study Thank you for your attention Konstantinos Chatzipapas 1 , Panagiotis Papadimitroulas 2 , Mohammad Ali Obeidat 3 , Neil Kirby 3 , George Loudos 4 , Niko Papanikolaou 3 and George C. Kagadis 1 (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
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