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Radiobiology &Radiobiology & Radiobiology of Accelerated Radiobiology of Accelerated

Heavy IonsHeavy Ions

Haitham A. ShabanHaitham A. Shaban

Assistant Researcher, NRCTeaching Assistant, American University in Cairo

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RADIOBIOLOGY:

THE STUDY OF THE EFFECTS OF IONIZING

RADIATION ON BIOLOGIC TISSUE

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RADIATION EFFECT CELL RADIATION EFFECT CELL THEORYTHEORY

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

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ATOMIC COMPOSITION OF ATOMIC COMPOSITION OF BODY:BODY:

• 80%• 25.7%• 10.7%• 2.4%• 0.1%• O.1%• 0.8%

02

H2

C

N2

P

S

TRACE ELEMENTS

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MOLECULAR COMPOSITION OF THE BODY

• 80%• 15%• 2%• 1%• 1%• 1%

WATER

PROTEIN

LIPIDS

CARBOHYDRATES

NUCLEIC ACID

OTHER

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Radiation Biology

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CELL RESPONSE TO RADIATION

• LYNPHOCYTES• SPERMATOGONIA

• OSTEOBLASTS• SPERMATIDS• MUSCLE CELL

• NERVE CELL

RADIOSENSITIVE

RADIORESISTANT

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RADIATION ENERGY TRANSFER DETERMINANTS

• LET

• RBE

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LET-LINEAR ENERGY TRANSFER

• THE AVERAGE ENERGY DEPOSITED PER UNIT LENGTH OF TRACK

keV/ μm

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LET

α

X-RAYS

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LETLET

• GAMMA RAYS

• X-RAYS

ALPHA PARTICLESIONS OF HEAVY

NUCLEICHARGED

PARTICLESLOW ENERGY

NEUTRONS

LOW LET HIGH LET

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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

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EFFECTS OF IONIZING RADIATION ON DNA

• BASE DAMAGE

• SINGLE STRAND BRAKE

• DOUBLE STRAND BRAKE

• CROSSLINKING

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Clustered DNA damages

Fragment of DNA

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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 MUTATION

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Radiation induced mutagenesisRadiation induced mutagenesis

Guanine

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SINGLE STRAND BRAKESRELATIVELY

INCONSEQUENTIAL IN TERMS OF CELL KILLING. WILL BE

EFFICIENTLY REPAIRED , WITH LITTLE, IF ANY,

LONG TERM CONSEQUENCES TO

THE CELL

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DOUBLE STRAND BRAKESVERY 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.

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CROSSLINKING

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Investigation of biological effects of accelerated heavy

ions forms the “new “new radiobiology”radiobiology”

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The JINR accelerators

LabEnergy

(up to)

ParticlesAccelerator

LNP660MeVProtonsPhasotron

LNR10MeV/amuHeavy ionsU-200

LNR50 MeV/amuHeavy ionsU-400M

LPHE6 GeV/amuProtons,

Heavy ions Nuclotron

LHE10 GeV/amuProtons,

Heavy ionsSinchro

phasotron

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The nuclotron beams

2.10710484Kr

10710656Fe

3.10810824Mg

7.10910912C

10101094He

10131010 - 1011p, d

In 2009Present statusBeam

Intensity (particles per cycle)

The maximal energy of particles up to 6 GeV/amu

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1 unit of the dose

1 unit of the dose

X-rays Fe ion

The dose distribution of radiation in matter

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What radiobiological problems can be solved at

use of the accelerated heavy particles?

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Heavy ions is a powerful tool for the solve of fundamental

problems of radiation genetics

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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

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PAC 08

LABORATORY OF RADIATION BIOLOGYLABORATORY OF RADIATION BIOLOGYLRB

0 1 2 3 4 5 60

10

20

30

40

50

60

70

80

90

mt

Time, h

Li - 40 ГрGamma - 40 Гр

0 1 2 3 4 50

5

10

15

20

25

30

35

40

45

50

mt

Доза, Гр

S G2 G0 G1

0 1 2 3 40

5

10

15

20

25

30

Mt

Доза, Гр

0 ч 24 ч 48 ч 72 ч 96 ч

Kinetics of DNA repair

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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.

fragment

2 chromosomes №1

29FMNH2+ RCHO + O2 FMN + RCOOH +H2O + h

luciferase

Induction of mutagenic DNA repair by heavy ionsInduction of mutagenic

DNA repair by heavy ions

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Stable chromosomal

aberration

Formation of stable chromosomal aberration after

heavy ion irradiation of human cells

-rays

Successful of cell division

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Formation of unstable chromosomal aberration after heavy

ion irradiation of human cells

Unstable chromosom

al aberration

Block of cell division

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Thanks to ASRT - EgyptThanks to ASRT - Egypt

Thanks to JINR - DubnaThanks to JINR - Dubna

Thanks to Prof. Е. А. Thanks to Prof. Е. А. KrasavinKrasavin

AcknowledgmentAcknowledgment

Thanks to ASRT - EgyptThanks to ASRT - Egypt

Thanks to JINR - DubnaThanks to JINR - Dubna

Thanks to Prof. Е. А. Thanks to Prof. Е. А. KrasavinKrasavin

Thanks to ASRT - EgyptThanks to ASRT - Egypt

Thanks to JINR - DubnaThanks to JINR - Dubna

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Thank you for the Thank you for the attention attention