Title: BIOLOGICAL EFFECTS OF IONIZING RADIATION AT MOLECULES AND CELLS
1BIOLOGICAL EFFECTS OF IONIZING RADIATION AT
MOLECULES AND CELLS
2The stage of action of ionizing radiation
3Effect of radiation on atom and molecules
4Effects of ionizing radiation at atomic level
Ionization
Excitation
5Mechananisms of damage at molecular level
6Direct 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)
7Indirect action of ionizing radiation
OH-
H
e-
O
H
X ray ? ray
H
Ho
P
OHo
8Radiolysis of H2O molecule
Shared electron
Shared electron
H-O-H ? H OH- (ionization) H-O-H ? H0
OH0 (free radicals)
9Reaction of H2O molecule radiolysis
?2? h? ? ?2? ?- ?2? h? ? ?2? ? ??
??? ?2? ?- ? ?-???? ? ?? ??- ?2? ?- ? ?2?
? ?? ??? ?2? ? ? ??? ?- ? ? ?? ?2? ??-
? ?2? ??? ?2? ?2? ? ?3? ??? ?3? ?- ?
?2? ??
10Effects 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)
11Reactions 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
12Lifetimes 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
13Relation 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
14Effect of radiation on biological molecules
15Biochemical reactions with ionizing radiation
- DNA is primary target for cell damage from
ionizing radiation
16Radiation induced DNA damage
17The 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
18Mechanisms of base excision and nucleotide
excision repair
19Mechanism of single-strand breaks DNA repair
Exonuclease
20DNA restoration failure
Unrejoined DNA double strand breaks
Incorrect repair of DNA damage
Cytotoxic effect
Mutations
21Radiation induced membrane damage
22Effect of radiation on cells
23Types of cellular damage
Norma
Mutation
repair
Changes of metabolism function
Interphase cell death
Mitotic cell death
24Cell cycle
25Radiosensitivity 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
26Mitotic death
NORMAL
IRRADIATED
27BergoniƩ and Tribondeaus law (1906)
- The most radiosensitive cells are
- actively proliferating (dividing) at the time of
exposure - undifferentiated (non-specialized in structure
and function)
28Interphase death
Why are peripheral blood lymphocytes highly
sensitive to radiation, although well
differentiated?
29Morphological 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
30Changes 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.
31Radiation induced chromosome damage
Chromosomes
32Radiation 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.
34Summary 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
35Lecture is ended
THANKS FOR ATTENTION
In lecture materials of the International Atomic
Energy Agency (IAEA), kindly given by doctor
Elena Buglova, were used