1 Radiobiology & Radiobiology of Accelerated Heavy Ions Haitham A. Shaban Haitham A. Shaban Assistant Researcher, NRC Teaching Assistant, American University in Cairo

2 RADIOBIOLOGY: THE STUDY OF THE EFFECTS OF IONIZING RADIATION ON BIOLOGIC TISSUE

3 RADIATION EFFECT CELL THEORY Radiation interaction at the atomic level can produce molecular change, as a result, cell will be produced deficient.

4 ATOMIC COMPOSITION OF BODY: 80% 25.7% 10.7% 2.4% 0.1% O.1% 0.8% 0 2 H 2 C N 2 P S TRACE ELEMENTS

5 MOLECULAR COMPOSITION OF THE BODY 80% 15% 2% 1% WATER PROTEIN LIPIDS CARBOHYDRATES NUCLEIC ACID OTHER

6 Radiation Biology

7 CELL RESPONSE TO RADIATION LYNPHOCYTES SPERMATOGONIA OSTEOBLASTS SPERMATIDS MUSCLE CELL NERVE CELL RADIOSENSITIVE RADIORESISTANT

8 RADIATION ENERGY TRANSFER DETERMINANTS LET RBE

9 LET-LINEAR ENERGY TRANSFER THE AVERAGE ENERGY DEPOSITED PER UNIT LENGTH OF TRACK keV/ μm

10 LET α X-RAYS

11 LET GAMMA RAYS X-RAYS ALPHA PARTICLES IONS OF HEAVY NUCLEI CHARGED PARTICLES LOW ENERGY NEUTRONS LOW LET HIGH LET

12 RBE –RELATIVE BIOLOGIC EFFECTIVENESS Relative capabilities of radiation with different LETs to produce particular biologic response. DOSE IN Gy FROM 250 KVP X-RAYS DOSE IN GRAY OF TEST RADIATION

13 EFFECTS OF IONIZING RADIATION ON DNA BASE DAMAGE SINGLE STRAND BRAKE DOUBLE STRAND BRAKE CROSSLINKING

14 Clustered DNA damages Fragment of DNA

15 BASE DAMAGE LOSS OR CHANGE OF A BASE ON DNA RESULTS IN ALTERATION OF THE BASE SEQUENCE. SEQUENCE OF THE BASE STORES GENETIC INFO- SERIOUS CONSEQUENCE TO THE CELL CLASSIFIED AS:MUTATION

16 Radiation induced mutagenesis Guanine

17 SINGLE STRAND BRAKES RELATIVELY INCONSEQUENTIAL IN TERMS OF CELL KILLING. WILL BE EFFICIENTLY REPAIRED, WITH LITTLE, IF ANY, LONG TERM CONSEQUENCES TO THE CELL

18 DOUBLE STRAND BRAKES VERY DIFFICULT FOR THE CELL TO BE REPAIRED. CAN LEAD TO CELL KILLING. IF REPAIR DOESN’T TAKE PLACE, THE DNA CHAINS CAN SEPARATE. SERIOUS CONSEQUENCE TO CELL LIFE.

19 CROSSLINKING

20 “new radiobiology” Investigation of biological effects of accelerated heavy ions forms the “new radiobiology”

21 The JINR accelerators LabEnergy (up to) Particles Accelerator LNP660MeVProtonsPhasotron LNR10MeV/amuHeavy ionsU-200 LNR50 MeV/amuHeavy ionsU-400M LPHE6 GeV/amuProtons, Heavy ions Nuclotron LHE10 GeV/amuProtons, Heavy ions Sinchro phasotron

22 The nuclotron beams Kr Fe Mg C He p, d In 2009Present statusBeam Intensity (particles per cycle) The maximal energy of particles up to 6 GeV/amu

23 1 unit of the dose X-raysFe ion The dose distribution of radiation in matter

24 What radiobiological problems can be solved at use of the accelerated heavy particles?

25 Heavy ions is a powerful tool for the solve of fundamental problems of radiation genetics

26 The RBE problem was solved at the Flerov Lab accelerators DNA repair capacity of the living cells determines the type of RBE on LET dependence block of DNA repair normal repair super fast repair Bacterial cells

27 PAC 08 LABORATORY OF RADIATION BIOLOGY LABORATORY OF RADIATION BIOLOGY Kinetics of DNA repair

28 3D dimension of human chromosome Chromosome 1 of human lymphocyte nucleus in interphase with fragment after irradiation 1 GeV protons at synchropha-sotron. The 3 D dimensi-on picture was obtained by using FISH technique and confocal microscopy. fragmen t 2 chromosomes №1

29 FMNH 2 + RCHO + O 2  FMN + RCOOH +H 2 O + h luciferas e Induction of mutagenic DNA repair by heavy ions

30 Stable chromosomal aberration  Formation of stable chromosomal aberration after heavy ion irradiation of human cells  -rays Successful of cell division

31  Formation of unstable chromosomal aberration after heavy ion irradiation of human cells Unstable chromosom al aberration Block of cell division

32 Thanks to ASRT - Egypt Thanks to JINR - Dubna Thanks to Prof. Е. А. Krasavin Acknowledgment Thanks to ASRT - Egypt Thanks to JINR - Dubna Thanks to Prof. Е. А. Krasavin Thanks to ASRT - Egypt Thanks to JINR - Dubna

33 Thank you for the attention