Laboratory of Radiation Biology, JINR Dr. Oleg Belov

Laboratory of Radiation Biology

What is the RADIOBIOLOGY?

Radiobiology (or radiation biology) is the complex fundamental science studying various aspects of influence ionizing and not ionizing radiations on biological objects

The fundamental problem of radiobiology:

the opening of general regularities of the organism's biological response to the influence of ionizing radiation

The basic radiobiological paradox Enormous discrepancy between the insignificant amount of the absorbed energy and the extreme expressiveness of biological object’s response up to a lethal outcome

The irradiation in a dose of 10 Gy kills mammals of all kinds

10 Gy = + 10 -3 0 С

Connection of radiobiology with other disciplines

Genetics Biology Biophysics Cytology Radiobiology Medicine Biochemistry Physiology Nuclear Physics

Phasotron

Protons with energy up to 660 MeV

U-400 M

Heavy ions 7 Li 2+  86 Kr 9+ Energy up to 50 MeV/amu

Synchrophasotron

Protons, heavy ions Energy up to 10 GeV/amu

Nuclotron

Heavy ions

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

A. Heavy ions is a powerful tool for solving problems in radiation genetics

Tracks of heavy ions in nuclear emulsion

Si Ca Ti Fe Z =14 20 22 26

Mammalian cell

Z = 70

Action of heavy ions can lead to the DNA damages

Z = 70

The dose distribution of radiation in matter

1 unit of the dose 1 unit of the dose X-rays Fe ion

А

DNA double strand breaks in human cells after X-ray (А) and heavy ion irradiation (B)

B

Single DNA damage Sparse ionizing radiation (X-rays) Single strand break Base damage Повреждени е основания Повреждение сахара

Clustered DNA damage Heavy ions irradiation Base damages

Double strand break of DNA

Sugar damage Base damages

Yield of clustered DNA damage as a function of Liner Energy Transfer ( LET )

1E-10 e 1 H 4 He 12 C 1E-11 1E-12 0,1 SSB + damage of opposite strand SSB + damage of opposite strand Base damage + sugar damage Base damage + sugar damage DSB DSB 1 10 L E T , keV/  m 100 1000

“Comet assay” for detection of DNA lesions

Dose, Gy D = 0 Gy D = 5 Gy D =10 Gy D = 20 Gy D = 40 Gy D = 60 Gy

Formation of unstable chromosomal aberration in human cells after heavy ion irradiation

Unstable chromosomal aberration

Dose, Gy Block of cell division

Formation of stable chromosomal aberrations in human cells after heavy ion irradiation

Chromosome № 1

Stable chromosomal aberration

Successful of cell division

Dose, Gy

B. Theoretical studies in Radiobiology

1. Theoretical study of induced mutagenesis

2. Simulation of particle track structure

Model of DNA Model of particle track

3. Molecular dynamics simulation of proteins structure

MDGRAPE-2 Board and Chip

4 MDGRAPE-2 chips PCI card 16 Mbyte SSRAM Broadcast write extension Prion 5 million transistors 0.25μm, 2.5 V from IBM corp.

15 Watt at 100 MHz clock frequency 15 Gflops equivalent RNA

C. Accelerated heavy ions as a tool for modeling of biological action of space radiation

Problem of manned interplanetary space missions

1 2

What will be the radiation environment during space flight?

… and at Mars?

The G alactic C osmic R ays flux

The integral flux of GCR particles of carbon and iron groups equals to

10 5 part/cm 2 per year

Particle flux density interplanetary space z  160 per day per cm 2 20

The energy spectrum of GCR and Nuclotron

Consequences of Galactic heavy ion action

 Induction of cancer;  Formation of gene and structural mutations;  Violation of visual functions: 

lesions of retina;



cataract induction;

 Central nervous system (CNS) violation

Worgul et al., 2006

In Vitro

Neurotoxic Effects of 56 Fe Ions on Retinal Explants

90000 70000 0

0 cGy 5 cGy 10 cGy

50000 0

50 cGy

30000 20000 0 50 100 Dose, cGy 150 200 250 apoptosis

100 cGy 200 cGy Vazquez, 2006

Cosmic ray hit frequencies in CNS critical areas A A B B CNS in General



2 or 13% cells will be hit at least one Fe particle



8 or 46% would be hit by at least one particle with Z



15



Every nucleus will be traversed by a proton once every 3 days and a alpha particle once every 30 days.

p p p Fe Mixed Field Multi-hit FE ION TRACKS VISUALIZED BY MARKERS OF DNA DSBs (γH2AX) 0 cGy 50 cGy



e TRACK DIRECTION 100 cGy 200 cGy

Control

Cognitive tests (Morris Water Maze)

56 Fe ions, 1 GeV/amu 1.5 Gy

1 month after irradiation

http://lrb.jinr.ru

Laboratory of Radiation Biology, JINR

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