Transcript Module 1 - International Atomic Energy Agency

Basics of Biological Effects of
Ionizing Radiation
Lecture
Module 1
IAEA
International Atomic Energy Agency
Biological effects of radiation
• Ionizing radiations have many beneficial applications,
but they also may have detrimental consequences for
human health and for environment
• Since X-rays were discovered in 1895, it was quickly
realized that they may be harmful
• To protect people and the environment it is essential
to understand how radiation-induced effects occur
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What is ionizing radiation?
A radiation can be considered as ionizing if deposited
energy is high enough to ionize the traversed material
Types
• electromagnetic (X and γ- rays)
• corpuscular (α- and β-particles and neutrons)
Each type interacts in its own way with material
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Absorbing ionizing radiation
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Interactions of ionizing radiation with
matter
Photons
For energies lower than 50 MeV there are
three main processes by which photons
interact with matter:
•
•
•
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Photoelectric effect
Compton scattering
Pair production
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Photoelectric effect.: incident photon is
totally absorbed and ejects electron from
atom. This effect dominates with lowenergy photons interacting with heavier
elements
In Compton scattering electron is also
ejected, but incident photon survives and is
scattered by losing some of its energy. In
water or biological tissues, this effect
dominates at energies above 50 keV
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Pair production is process in which its
energy is converted into electron-positron
pair. This interaction starts occurring at
energies higher than 1 MeV. Unlike
electron, positron will eventually disappear
annihilating one electron of surrounding
material. Positron-electron pair is
converted into two photons with energy of
about 0.5 MeV
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Neutrons
Neutrons interact with nuclei (elastic and inelastic diffusion,
nuclear reactions, captures), and produce emission of
secondary charged particles (like protons, alpha particles
or nuclear fragments heavier than carbon, oxygen, nitrogen
or hydrogen) which are responsible for tissue ionization
++
and for biological effect
+
+
elastic diffusion with
production of proton and
another neutron
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collision with nucleus with the
production of various charged
particles: protons, nuclear
fragments, electrons
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Charged Particles
• These interact with nuclei (nuclear interactions) and to
greater extent with electrons (electronic interactions)
• As they slow down energy deposited per depth unit (or
LET) increases until particle comes to halt, and there is
sudden peak of energy (Bragg peak)
Relative ionization with depth
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Units of radioactivity
Radioactive decay is process by which atomic nucleus of unstable atom
loses energy by emitting ionizing particles (ionizing radiation)
Radioactive decay is stochastic process at level of single atoms and
chance that given atom will decay is constant over time, so that given
large number of identical atoms (nuclides), the decay rate for collection is
predictable to extent allowed by law of large numbers
Important measure is the ACTIVITY
SI unit of activity is becquerel (Bq). 1 Bq is defined as one transformation
(or decay) per second. Former unit of radioactivity was curie (Ci):
1 Ci is equal to 3.7 × 1010 Bq
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Examples of radioactive decay
Cobalt-60 decay emitting a
b-particle
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Radium-26 decay emitting
an a-particle
Images from:
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http://www.flickr.com/photos/mitopencourseware
Number of radioactive atoms
decreases by exponential decay
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Image from: http://www.flickr.com/photos/mitopencourseware
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Quantities used in radiation studies
Amount of radiation producing effect is specified as energy
deposited per unit mass in irradiated material. This is
absorbed dose (D)
D  
m
Where  is energy absorbed in mass m. This is
measured as J/kg and SI unit is gray (Gy)
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However, each type deposits its energy in different way
Linear energy transfer (LET) is measure of energy transferred by ionizing
particle to traversed material. This measure is typically used to quantify
effects of ionizing radiation on biological specimens and is usually
expressed in units of keV/µm
Low-LET
•X and -rays are sparsely ionizing radiations
•Energy is distributed homogeneously
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High-LET
•-, -particles and neutrons and densely
ionizing radiations.
•The energy is distributed
inhomogeneously
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High LET radiation types are more efficient in
producing damage
To normalize the Relative Biological Effectiveness is used
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Relationship between RBE and LET
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Equivalent Dose
• Equivalent absorbed radiation dose (equivalent
dose) - computed average measure of radiation
absorbed by fixed mass of biological tissue
• accounts for different biological damage
potential of different types of ionizing radiation
on different organs, considering differences in
their RBE
• Equivalent dose is a judged quantity for
assessing health risk of radiation exposure
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Equivalent Dose
• Equivalent dose cannot be measured directly. Dose for each tissue T
and each type of radiation R (often denoted by HT,R) is calculated by:
HT,R = Q x DT,R
where DT,R is total energy of radiation absorbed in unit mass of tissue T,
and Q is radiation quality factor that depends on type and energy of
that radiation. Quality factor is related to relative biological
effectiveness of radiation
• SI unit for equivalent dose is severt (Sv) - dose of absorbed radiation, in
Gy, that has same biological effect as dose of one joule of gamma rays
absorbed in one kilogram of tissue
• Sv has replaced the previous unit rem (roentgen equivalent man):
100 rem = 1 Sv
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Radiation quality or weighting factors
Radiation Type
Energy
W (ICRP-60)
W (ICRP-92)
Photons
all
1
1
Electrons,
muons
all
1
1
Neutrons
<10 keV
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function
Neutrons
10-100 keV
10
function
Neutrons
>100 keV- 2Mev
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function
Neutrons
>2 -20 MeV
10
function
Neutrons
>20Mev
5
function
Protons
<2 MeV
5
2
α-particles,
fission
fragments
all
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ICRP-60 (1991), ICRP-92 (2004)
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Chromosomal structure
Association of DNA and
histones in nucleosome
structure has been
demonstrated in
considerable detail. DNA is
external to the histone core
of nucleosome. Some
studies support existence of
axial core structure formed
by non-histone proteins or
non-histone protein scaffold
in metaphase chromosome
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Human karyotype
Human karyotype - characteristic complement for humans, and consists of 23
pairs of large linear chromosomes of different sizes, giving total of 46
chromosomes in every diploid cell. Human chromosomes are normally
combined into seven groups from A to G plus pair of sex chromosomes X and Y.
Chromosomal groups are: A:1-3, B: 4 and 5, C: 6 -12, D: 13-15, E: 16-18, F: 19
and 20 and G: 21 and 22.
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Male
Female
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Energy deposited in and near DNA
Ionizing radiation produces
discrete energy deposition
events in time and space
DNA is damaged directly and
indirectly by generation of
reactive species mainly
produced by radiolysis of
water
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• Direct action of radiation is dominant process for high–LET, such
as neutrons or α-particles
• For low-LET radiation, direct action represents about 20%, and
indirect action is about 80%. Radiolysis of water produces free
radicals (atoms or molecules with unpaired electrons that are highly
reactive). Free radicals are usually denoted by a dot (•)
• Radiolysis of water generates water radical and electron (1). Electron
may still have enough energy to cause further ionizations in
neighbourhood. Ionizing radiation can also cause excitation events (2)
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H2O
H2O•+ + e- (1)
H2O
H2O*
(2)
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• Water radical cation is very strong acid that loses proton to neighbouring
water molecule and forms OH radical which is oxidizing agent (3, 4), that is
probably the most damaging radical
H2O •+ + H2O
H2O •+
H3O+ + •OH
(3)
•OH
(4)
+ H+
• Electron becomes hydrated by water (5) and electronically excited water
can decompose into •OH and H• (6). So, three kinds of free radicals are
initially formed •OH , H• , and e-aq
e- + H 2 O
H 2 O*
e- aq
•OH
(5)
+ H•
(6)
• Globally, and after further reactions, radiolysis of water in presence of
oxygen produces: •OH, e- aq, H• , O2 •-, H2O2, H2.
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Damage in DNA
• Low-LET radiation can
produce localized cluster of
ionizations within single
electron track
• High-LET radiation produces
somewhat larger number of
ionizations that are closer
together
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Types of DNA lesions
Estimation of numbers of
radiation - induced
different types of DNA
lesions after 1 Gy
irradiation with low-LET
radiation
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Cell has complex signal transduction, cell-cycle checkpoint and
repair pathways to respond to DNA damage
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Cell cycle and checkpoints
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DSB are critical DNA lesions. Their mis-repair or non-repair leads to
formation of aberrations like dicentrics.
There are two main mechanisms to repair DSB: Homologous recombination
(HR) and non-homologous end-joining (NHEJ)
Two mechanisms operate in different phases of cell cycle. NHEJ occurs mainly in
the quiescent G0 phase and during cell cycle in G1 but can also occur in later
phases. HR can occur only when DNA is replicated, in S and G2 phase.
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Non-homologous end joining
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