.

F

() ( )

() . () .

.

( ) .

, .

(100%).

, , , , .

, ( ) , :

1. . , .

2. (.. 1 sec) (.. 1 ).

3.

, , , , ..

, , :

1. , ( ).

2. , (.. ) .

3. , , (patterns) .

:

- ( )

- ( ) ( ) .

, .

) L.E.T. (Linear Energy Transfer) ) (R.B.E.).

,

.

L.E.T.

L.E.T. (Linear Energy Transfer) dE, ( ) dx.

LET ( KeV/m) . LET DNA, .

LET < 10 KeV/m LET, LET > 10 KeV/m LET.

L.E.T. = dE/dx

L.E.T.

L.E.T. (KeV.m-1)

50 KV X 13,1

200 KV X 9,4

Co-60 6,9

2 MV X 6,1

22 MV X 6,0

5,3 MV 63,0

H L.E.T. . R.B.E. (Relative Biological Effectiveness). rem, 1 rem = 1 rad x R.B.E.

R.B.E.

(R.B.E.) L.E.T. ( , 60 120 eV) .

R.B.E. , (.. , , , ).

R.B.E.

RBE : (

) (.. LET)

(endpoint), .. ,

( , LET).

R.B.E. L.E.T. 100 KeV/m R.B.E. L.E.T.

L.E.T. .

L.E.T., , R.B.E. .

RBE LET

, .

.

, () 2h 24-48h. G0 - G1, S G2

DNA S (Synthesis).

G2 , .

( M), , , DNA, .

G1 (Gap), , . G0. G0 . G1 , RNA DNA .

.

, .

, G2. G2 arrest ().

2 mm 200 nm

20 nm

2 nm

DNA. ( )

SSB

10-20 - 10-8 s

DNA. ( )

DSB

10-20 - 10-8 s e-

. ( )

H2O H2O+ + e-

H+ + OH 10-18 - 10-9 s

80-85%

H2O

, :

,

-,

.

( ), ( ).

L.E.T. , m, L.E.T. m. (.. , Compton).

10-16 10-12 s.

-

, 2 ( ), .

2 ( 20 40 kJ/mole) , 2 (2,5 kJ/mole).

C-C, C-H, C-N, C-P C-O.

5 7 eV. , 100 KeV , 100 eV 14.000 20.000 .

, .

-

-

-

.

, .

- , .

, , ( ), , .

-

:

1. , - . (DNA , RNA) .

-

2. , , , , 2 ( ).

3. , . , ( ).

-

:

mm, , DNA .

. , 85% 15% .

To - 10-4 10-3 s.

, ( RH):

RH RH+ Ro + H+

, , ..:

Ro + O2 RO2o

e-

, 2:

H2O HOH+ + e-

10-12 ( , eaq):

H2O HOH+ + eaq

- HOH-

+ - +, - , .

HOH+ H+ + OHo

HOH- Ho + OH-

: H+ + OH- H2O

, (10-5 s 2), , . .

Ho, OHo

, :

OHo + OHo H2O2

2 :

Ho + O2 HO2o

: HO2o + HO2

o H2O2 + O2

, :

RH + Ho Ro + H2

RNH2 + Ho Ro + NH3

e- DNA. ,

, , .

RCH = CHR + OHo RCHOH - CHoR

DNA 4 : (), (G), (T), (C). .

(.. R1

o + R2o -> R1 R2),

, , , .

.

.

.

DNA.

H DNA .

DNA, , , , .

DNA

DNA

Sv

(Double Strand Brake) 50

(Single Strand Brake) 50-1000

1000-2000

800-1600

DNA-DNA 30

DNA- 150

DNA Sv

.

. , , .

Sv

(Double Strand Brake) 50

(Single Strand Brake) 50-1000

1000-2000

800-1600

DNA-DNA 30

DNA- 150

DNA Sv

( ) , .

.

, , .

in vivo in vitro , (.. ) .

( ).

.

, .

.

, ( ).

( ), .

.

, .

(.. ).

() , , .

, , .

, , RNA.

, , .

, , .

:

. ,

.

.

.

, .

.

.

.

.

G1 DNA ( S).

.

, , :

- ( ), - , - (

).

.

, , .

:

. , . . .

.

.

.

.

.

.

.

.

.

.

1 106 10 mSv.

.

.

( ) .

:

.

,

.

-

.

.

:

. ,

.

.

.

:

.

.

.

-, Go.

(< 500 mSv), . - .

.

.

:

(.. , )

:

, .

.

100 Sv .

.

.

.

, .

.

.

(.. , ) , , , .

50 5 6 (25=32, 26=54). RNA DNA, , , .

. .

G2 S,

- . .

,

:

, .

. Sv .

, 15 Sv, 50% , 24 10 Sv.

.

, . -. - , .

, , . .

:

H (quanta). .

, . .

.

:

, , , ( ) .

, , ( ) .

. , .

. D1 D0 . A 37% .

. , Bergonie Tribondeau (1906) .

Bergonie Tribondeau, :

. (.. ) , .

. .

:

. (stem cells)

.

. : ,

.

. .

, ( , ). . , .

(Sv) -

2 10

10 20

20 30

-

30 40

40 50

50 60

60 70

, , , .

/ . : , , , .

, .

, .

.

F

(hierarchial) F (flexible) :

,

(, ...)

F,

(.. , , )

F, .

, , .

F

, , - (.. , , , ).

- ( ), .

H , , .. , .

(...)

,

F

, .

, (..)

( ) (1 Sv) :

(10 Sv) ... ( )

( )

()

... ()

1 Sv * 5 Sv ** 20 Sv ***

> 2 Sv > 10 Sv > 50 Sv

1 2

2 3 3 5 15 3

( )

3 8 3

2 2

-

+

(...) ...

, , , , , , 27 36 ( ). .

, , . .

, , .

* 10.000 20.000 (1 / = 5 100 Sv) ** 50.000 100.000 *** 200.000 400.000 +

4: , (, 1991)

,

, ,

,

, , ,

, .

:

, :

( 6 ) , 10 .

(2 3 ) , 20 30 .

, .

(Sv)

( )

2 52

15 4

15 6 10

18 >10

20 >6

, (.. ).

, 6 8 .

:

,

, 1,7 6,4 Sv 3,2 10 Sv ( )

, 100 mSv,

, 100 150 mSv 2 Sv. , .

(Sv)

Leydig 0,5

> 0,5

4

> 1

18

> 18

2

2

8 11

12

12

10

40

0,5

(, 1997)

. .

: () (

)

()

/

1 Sv

(I.C.R.P., 1977)

/ 10 mSv

(U.N.S.C.E.A.R., 1977)

( ) 10-2 10-4

2 x 10-3 20-50 x 10-6

2 x 10-3 25-50 x 10-6

2,5 x 10-3

10-5

( 35-49 ) 60 x 10-6

( 19-34 )

0,5 x 10-3 2-5 x 10-6

0,5 x 10-3 5-15 x 10-6

5 x 10-3

30 25

PTV

, .

15% , , 40% .

.

PTV

10

30

50

70

90

100

20 1020

PTV

PTV

10

30

50

70

90

100

20 1020

PTV

. .

G2 S,

- . . ,

, Elkind & Sutton 1959, : .

R. Withers 4 R , R 5

1. (Repair), 2. (Repopulation), 3. (Redistribution), 4. (Reoxygenation) 5. (Radiosensitivity)

1. (Repair)

.

, .

2. (Repopulation)

, , . 3 :

) .

) (growth fraction).

) (cell loss factor).

. , , .

3. (Redistribution)

.

G2, S. . , , G2.

. , , .

4. (Reoxygenation)

. , , .

, , , .

( , , -, - ..) .

5. A (Radiosensitivity)

(Radiosensitivity), .

3 :

) ,

)

) .

.

, .

.

(clonogenic cell death) , .

, , (D < 5 Gy)

(single hit injury) , . - , n :

/ 0( ) 1 (1 )D D n

SHMTS D e

, Elkind Sutton, . - ( LQ) '60 . LQ , DNA . LQ :

2

( ) D DLQS D e

2 : () .

(LQ), . ( ) . 1-2 Gy/ . (-, ).

. .

. (..) - : .. = exp (2d2). .

(.. SF=0,01) , . . , - .

(Linear Energy Transfer LET) .

10 5-7 nm. DNA ( 2 nm) 20 .

LMDS (Local Multiple Damage Sites). .

(Double Strand Break - DSB), (Single Strand Break - SSB) . : SSB BSB LMDS.

/

/, .

/ ,

/2)()(2

dddee dd

.

, .

. , , .

. , , .

.

, , , .

1.8-2 Gy .

1.8-2 Gy, 1.1-1.3 Gy. 10-15% .

, , 2 3 . .

.

:

1. . .

2. , .

3. 4 , 6 , .

, .

, , .

, :

) , ,

) .

.

TCP (Tumour Control Probability)

NTCP (Normal Tissue Complication Probability)

-

-

-

-

2500

/ ln ln 2( ) exp exp

D D e e nd ndP D N e e

- (LQ)

- :

1. H Poisson

2. - ( ).

3. 4.

.

, (Functional Sub Units).

FSUs , .

FSUs :

1. 2. , 3. .

(Relative Seriality Model) LKB

, , ( s) .

1/

I

1

[1 (1 ( ) ) ]iM

vs s

i

i

P P D

LKB

, , n .

vi

.

.

.

.

.

.

Di

VEFF

LKB

, , n .

1/

LKB

tot

EUD ( )n niii

VD

V

1

1

parallel 50

tot50

1EUD ([ ] 1)

1 ( / )

i k

ki i

VD

VD D

2

21

NTCP2

t x

e dx

: t = (EUD-TD50 )/ m*TD50

, :

) ( )

) ( )

) ( )

, .

.

.

/