Radiobiology Radiobiology of Accelerated Heavy Ions Haitham A

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

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

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

ATOMIC COMPOSITION OF BODY: • • 80% 25. 7% 10. 7% 2. 4% 0. 1% O. 1% 0. 8% 02 H 2 C N 2 P S TRACE ELEMENTS 4

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

Radiation Biology 6

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

RADIATION ENERGY TRANSFER DETERMINANTS • LET • RBE 8

LET-LINEAR ENERGY TRANSFER • THE AVERAGE ENERGY DEPOSITED PER UNIT LENGTH OF TRACK ke. V/ μm 9

LET α X-RAYS 10

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

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 12

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

Clustered DNA damages Fragment of DNA 14

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

Radiation induced mutagenesis Guanine 16

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

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. 18

CROSSLINKING 19

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

The JINR accelerators Accelerator Particles Energy (up to) Lab Phasotron Protons 660 Me. V LNP U-200 Heavy ions 10 Me. V/amu LNR U-400 M Heavy ions 50 Me. V/amu LNR Protons, Sinchro Heavy ions phasotron Protons, Nuclotron 10 Ge. V/amu LHE 6 Ge. V/amu LPHE Heavy ions 21

The nuclotron beams Intensity (particles per cycle) Beam p, d 4 He 12 C 24 Mg 56 Fe 84 Kr Present status 1010 - 1011 109 108 106 104 In 2009 1013 1010 7. 109 3. 108 107 22 The maximal energy of particles up to 6 Ge. V/amu

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

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

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

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

LABORATORY OF RADIATION BIOLOGY Kinetics of DNA repair 27 PAC 08

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

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

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