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BIOLOGICAL EFFECTS OF IONIZING RADIATION AT MOLECULES AND CELLS

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Title: BIOLOGICAL EFFECTS OF IONIZING RADIATION AT MOLECULES AND CELLS


1
BIOLOGICAL EFFECTS OF IONIZING RADIATION AT
MOLECULES AND CELLS
2
The stage of action of ionizing radiation
3
Effect of radiation on atom and molecules
4
Effects of ionizing radiation at atomic level
Ionization
Excitation
5
Mechananisms of damage at molecular level
6
Direct action of ionizing radiation
Ionizing radiation RH R- H
Bond breaks
?
?
O II R C NH2 amide (ketol)
Tautomeric shifts
OH I R C NH imidol (enol)
7
Indirect action of ionizing radiation
OH-
H
e-
O
H
X ray ? ray
H
Ho
P
OHo
8
Radiolysis of H2O molecule
Shared electron
Shared electron
H-O-H ? H OH- (ionization) H-O-H ? H0
OH0 (free radicals)
9
Reaction of H2O molecule radiolysis
?2? h? ? ?2? ?- ?2? h? ? ?2? ? ??
??? ?2? ?- ? ?-???? ? ?? ??- ?2? ?- ? ?2?
? ?? ??? ?2? ? ? ??? ?- ? ? ?? ?2? ??-
? ?2? ??? ?2? ?2? ? ?3? ??? ?3? ?- ?
?2? ??
10
Effects of oxygen on free radical formation
Oxygen can modify the reaction by enabling
creation of other free radical species with
greater stability and longer lifetimes H0 O2 ?
HO20 (hydroperoxy free radical) R0 O2 ? RO20
(organic peroxy free radical)
11
Reactions with free radicals
H0 OH0 ? H2O H0 H0 ? H2 OH0 OH0 ? H2O2
RH OH0 ? R0 H2O RH H0 ? R0 H2 R0 OH
? ROH R0 H ? RH R0 O2 ? ROO0 ROO0 RH ?
ROOH R0
12
Lifetimes of free radicals
HO2o
RO2o
Ho
OHo
3nm
OHo
Ho
Because short life of simple free radicals
(10-10sec), only those formed in water column of
2-3 nm around DNA are able to participate in
indirect effect
13
Relation between linear energy transfer (LET) and
type of action
  • Direct action is predominant with high LET
    radiation, e.g. alpha particles and neutrons
  • Indirect action is predominant with low LET
    radiation, e.g. X and gamma rays

14
Effect of radiation on biological molecules
15
Biochemical reactions with ionizing radiation
  • DNA is primary target for cell damage from
    ionizing radiation

16
Radiation induced DNA damage
17
The most important types of radiation induced
lesions in DNA
Base damage 1000-2000 per 1 Gy
Single-strand breaks 500-1000 per 1 Gy
Double strand breaks 40-50 per 1 Gy
18
Mechanisms of base excision and nucleotide
excision repair
19
Mechanism of single-strand breaks DNA repair

Exonuclease
20
DNA restoration failure
Unrejoined DNA double strand breaks
Incorrect repair of DNA damage
Cytotoxic effect
Mutations
21
Radiation induced membrane damage
22
Effect of radiation on cells
23
Types of cellular damage
Norma
Mutation
repair
Changes of metabolism function
Interphase cell death
Mitotic cell death
24
Cell cycle
25
Radiosensitivity of cell in cell cycle
M G1 S
G2 M
Relative survivability of cells irradiated in
different phases of the cell cycle synchronised
cells in late G2 and in mitosis (M) showed
greatest sensitivity to cell killing
26
Mitotic death
NORMAL
IRRADIATED
27
BergoniƩ and Tribondeaus law (1906)
  • The most radiosensitive cells are
  • actively proliferating (dividing) at the time of
    exposure
  • undifferentiated (non-specialized in structure
    and function)

28
Interphase death
Why are peripheral blood lymphocytes highly
sensitive to radiation, although well
differentiated?
29
Morphological forms of cell death
  • Pyknosis The nucleus becomes contracted,
    spheroidal, and filled with condensed chromatin.
  • Karyolysis The nucleus swells and loses its
    chromatin.
  • Protoplasmic Coagulation Irreversible gelatin
    formation occurs in both the cytoplasm and
    nucleus.
  • Karyorrhexis The nucleus becomes fragmented
    and scattered throughout the cell.
  • Cytolysis Cells swell until they burst and
    then slowly disappear.
  • Apoptosis Programmed cell death, usually be
    fragmentation

30
Changes of cell metabolism and function
  • Block of Mitotic Cycle Mitosis may be delayed
    or inhibited following radiation exposure.
  • Disruptions in Cell Growth Cell growth may also
    be retarded, usually after a latent period.
  • Permeability Changes Irradiated cells may show
    both increased and decreased permeability.
  • Changes in Cell Motility The motility of a cell
    may be decreased following irradiation.

31
Radiation induced chromosome damage
Chromosomes
32
Radiation induced chromosomal aberrations
33
Relative cellular radiosensitivity
  • Vegetative Cells these cells, comprising
    differentiated functional cells of a large
    variety of tissues, are generally the most
    radiosensitive.
  • Differentiating Cells these cells are somewhat
    less sensitive to radiation they are relatively
    short-lived and include the first generation
    produced by division of the vegetative mitotic
    cells.
  • Totally Differentiated Cells these cells are
    relatively radioresistant they normally have
    relatively long lifespans and do not undergo
    regular or periodic division in the adult stage,
    except under abnormal conditions such as
    following damage to or destruction of a large
    number of their own kind.
  • Fixed Nonreplicating Cells these cells are most
    radioresistant they are highly differentiated
    morphologically and highly specialized in
    function.

34
Summary of lection
  • Cells going through the division phase (M and S)
    are generally the most sensitive to ionizing
    radiation. Exceptions lymphocytes and some bone
    marrow stem cells, which exhibit interphase death
  • Bone marrow consists of progenitor and stem
    cells, the most radiosensitive cells in the human
    body and the most important in controlling
    infection

35
Lecture is ended
THANKS FOR ATTENTION
In lecture materials of the International Atomic
Energy Agency (IAEA), kindly given by doctor
Elena Buglova, were used
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