Basics of Biological Effects of Ionizing Radiation

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Basics of Biological Effects of Ionizing Radiation

• Lecture
• Module 1

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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

• electromagnetic (X and ?- rays)
• corpuscular (a- and ß-particles and neutrons)

Types
Each type interacts in its own way with material
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
• 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 low-energy 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
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)

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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) Radioacti
ve 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
Radium-26 decay emitting an a-particle

Images from http//www.flickr.com/photos/mitopenc
ourseware
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Number of radioactive atoms decreases by
exponential decay
Image from http//www.flickr.com/photos/mitopenco
urseware
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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)
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
High-LET
Low-LET

• ?-, ?-particles and neutrons and densely ionizing
  radiations.
• The energy is distributed inhomogeneously

• X and ?-rays are sparsely ionizing radiations
• Energy is distributed homogeneously

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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 lt10 keV 5 function
Neutrons 10-100 keV 10 function
Neutrons gt100 keV- 2Mev 20 function
Neutrons gt2 -20 MeV 10 function
Neutrons gt20Mev 5 function
Protons lt2 MeV 5 2
a-particles, fission fragments all 20 20
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
A1-3, B 4 and 5, C 6 -12, D 13-15, E 16-18,
F 19 and 20 and G 21 and 22.
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 highLET, such as neutrons or a-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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• 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

• 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

• 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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