TRACKS IN PHYSICS AND BIOLOGY Hooshang Nikjoo Radiation Biophysics Group Department of Oncology pathology Karoloinska Institutet

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TRACKS IN PHYSICS AND BIOLOGY Hooshang Nikjoo Radiation Biophysics Group Department of Oncology pathology Karoloinska Institutet Some Questions in Radiation Physics, Biology, and Protection: How much

1 TRACKS IN PHYSICS AND BIOLOGY Hooshang Nikjoo Radiation Biophysics Group Department of Oncology pathology Karoloinska Institutet Some Questions in Radiation Physics, Biology, and Protection: How much better is radiotherpay with ions than electrons and photons? New modalities in radiation therapy such as use of Internal Emitters Risk from exposure to low doses of ionizing radiation Estimation of genetic risk based on human data Impact of radiation exposure on vasculature and CNS Role of Systems Biology in radiation biology Are cell signaling after low and high LET damage the same?

3 Environmental exposure to natural background radiations: 2.4 msv/year Low-LET exposure from ingestion 7% Low-LET exposure from earth 20% High-LET radon exposure 52% Low-LET cosmic photon radiation exposure 12% High-LET cosmic radiation 4% Data: BEIR VII 2006, UNSCEAR 2000 High-LET exposure from ingestion 5%

6 Appx. Radiation Doses in the Environment Natural radiations: Annual work limit: ISS: MARS surface: Space: Radiotherapy: Transatlantic travel: CT scan ~ 6.7 µsv/d <20 msv/yr (ICRP) ~0.5 msv/d ~ 0.75 msv/d ~1.5 msv/d ~2 Gy/d ~0.05 msv ~ msv

8 Typical doses and number tracks in cell nucleus Target Radiation Dose (mgy) Q-Factor Dose Equivalent (msv) Ave # of tracks per cell nucleus Whole body Low LET ~1 Lung High LET ~0.001 Bone Marrow High LET ~ Workers Whole body Low LET < High LET < Neutrons (1MeV) <

9 The Problem Risk from low doses of ionizing radiation

10 What is the risk of cancer from exposure to low-let radiation? Exposure to Terrestrial Natural Background Radiation: Average Annual Exposure (1-10 msv) <2.4 msv/yr> (low-let) 0.9 (39%) (high-let) 1.5 (61%) Cancer Expected to develop Risk of Death All 42% 22.8% Leukemia & SC (0.1Sv) 1% BEIRVII Report suggests approximately one cancer per 100 people could result from a single exposure to 0.1Sv of low-let radiation above the background

11 S

12 Physics and Simulation of Radiation Track at Molecular Level Uehara & Nikjoo 2006

13 Interactions for Low-Energy H + and H 0 in Water Interactions H + + H 2 O H 0 + H 2 O Elastic scattering H + + H 2 O H 0 + H 2 O Target ionization H + + H 2 O + +e H 0 + H 2 O + +e Target excitation H + + H 2 O* H 0 + H 2 O* Electron capture H 0 + H 2 O + (σ 10 ) - Electron loss - H + +e + H 2 O (σ 01 ) Interactions for Low-Energy He 2+, He + and He 0 in Water Interactions He 2+ + H 2 O He + + H 2 O He 0 + H 2 O Elastic scattering He 2+ + H 2 O He + + H 2 O He 0 + H 2 O Target ionization He 2+ + H 2 O + +e He + + H 2 O + +e He 0 + H 2 O + +e Target excitation He 2+ + H 2 O* He + + H 2 O* He 0 + H 2 O* Two-electron capture He 0 + H 2 O 2+ (σ 20 ) - - One-electron capture He + + H 2 O + (σ 21 ) He 0 + H 2 O + (σ 10 ) One-electron loss - He 2+ +e +H 2 O (σ 12 ) He + +e +H 2 O (σ 01 ) Two-electron loss - - He 2+ +e+e +H 2 O (σ 02 ) Uehara & Nikjoo 2002 Uehara et al 2002, 2001

14 Physics and Simulation of Radiation Tracks of Ions at Molecular Level Radiation Depth at Dose Gy cm 2 Fluence for Track #per cell 1 cgy /cm 2 nucleus 60 Co γ rays 5 mm 5.8 x MeV proton Bragg peak 4.7 x Liamsuwan, Uehara, Nikjoo 2010 Nikjoo et al 2008

15 Number of events in a 200 MeV full slowing down proton track p p p p H H H H Secondary electrons ionization ( ev) ionization ( ev ionization ( ev) ionization ( ev) ionization (539.7 ev) excitation excitation excitation excitation excitation excitation excitation excitation sub-excitation electrons elastic scattering ionization excitation e-capture elastic scattering ionization excitation electron loss ev ev ev ev ev A 1 B 1 B 1 A 1 Rydberg A+B Rydberg C+D diffuse band H* Lyman a H* Balmer a OH* 200,908 1,943,795 1,117,797 1,294 2,259 1, ,293 1,977,465 1,494, ,941 20,812 7, , , , ,007 1,204, ,570 67, , ,450 Nikjoo et al 2010

16 Interaction of Radiation with Matter Physics and Simulation of Low Energy Electrons Dielectric response function represents how strongly the medium absorbs light as a function of wavelength (Oscillator Strength Distribution) material properties: absorbance, reflectance, etc generalized phenomenon ε ( w) = ε ( w) + iε ( w) 1 2 ε ( w, q) = ε ( w, q) + iε ( w, q) 1 2

17 Background Low energy electrons (<1 kev) are of fundamental importance to track structure studies because they are abundantly produced and exhibit a densely energy loss pattern in matter. More than 75% of biological damage arise from LEE<1keV ev; more than 90% from LEE<50eV Presently, most inelastic calculations are based on extendedoptical data (EOD) dielectric models because they are: (i) suitable for any type of material (conductor, semiconductor, insulator), (ii) applicable over a wide energy range, and (iii) of relatively low computational cost. The Problem Most EOD models fail at low electron energies (< ev) because they neglect the momentum broadening and shifting of the Bethe ridge.

18 Bethe-Ridge Surface Emfielzoglou et al 2005

19 In 1997 the Japanese group extended their IXS measurements to the whole Bethe surface of liquid water providing, for the first time, evidence for the q dependence of the dielectric function. In 2005, Emfietzoglou, Cucinotta, and Nikjoo (ECN) published an extended Drude model that fits fairly accurately the IXS data over the measured E q plane. RadRes 2005

20 Electron stopping power in liquid water Emfietzoglou and Nikjoo 2010

21 The Problem Determining spectrum of DNA damage after repair

22 DNA damage-repair Watanabe&Nikjoo 2001 Nikjoo et al 2003 Nikjoo et al 2001

23 Models of DNA Damage-Repair SSA, HR, NHEJ + (BER & Cell Cycle) Taleei, Weinfeld, Nikjoo 2010

24 DSB REPAIR Taleei et al 2010

25 CONCLUSIONS Advances in Monte Carlo track structure simulations have made it possible to elucidate concepts in: dosimetry, differences between low and high LET radiations, model types & quantify simple and complex DNA damage, dosimetry of radionuclides, and radioprobing of novel DNA structures. Most radiation-induced mutations are large multi-gene deletions The principal phenotypes of viability-compatible deletions induced in germ cells are more likely to be multi-system developmental abnormalities rather than single gene diseases

26 Radiation Biophysics Group Peter Girard Reza Taleei Thiansin Liamsuwan Tommy Sundstrom Radioprobing/Telomere Structure DNA Damage-Repair Physics and track simulation Information Technology Associate Members Dimitris Emfietzoglou Medical Physics, Ioannina Medical School K. Sankaranarayanan Toxicogenetics Department, Leiden Lennart Lindborg RBG, Karolinska Institutet, Stockholm Shuzo Uehara School of Health Sciences, Kyushu RBG work is supported by SSM and KI

Radioactivity. Lecture 7 Dosimetry and Exposure Limits

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