module 1_basics of biological effects of ionizing radiation

8/12/2019 Module 1_Basics of Biological Effects of Ionizing Radiation

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IAEAInternational Atomic Energy Agency

Basics of Biological Effects ofIonizing 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 forhuman 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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Absorbing ionizing radiation

What is ionizing radiation?

electromagnetic (X and - rays)

corpuscular (- and -particles and neutrons)

A radiation can be considered as ionizing if depositedenergy is high enough to ionize the traversed material

Types

Each type interacts in its own way with material

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Interactions of ionizing radiation with

matter

Photons

For energies lower than 50 MeV there are

three main processes by which photonsinteract with matter:

Photoelectric effect

Compton scattering Pair production

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Photoelectric effect.:incident photon istotally absorbed and ejects electron from

atom. This effect dominates with low-

energy photons interacting with heavier

elements

InCompton scattering electron is also

ejected, but incident photon survives and is

scattered by losing some of its energy. Inwater 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. Unlikeelectron, positron will eventually disappear

annihilating one electron of surrounding

material. Positron-electron pair is

converted into two photons with energy ofabout 0.5 MeV

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Neutrons

Neutrons interact with nuclei (elastic and inelastic diffusion,

nuclear reactions, captures), and produce emission ofsecondary 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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Radioactive decay is process by which atomic nucleus of unstable atomloses 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 ispredictable 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 1010Bq

Units of radioactivity

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IAEA Images from:http://www.flickr.com/photos/mitopencourseware

Cobalt-60 decay emitting a

b-

particle

Examples of radioactive decay

Radium-26 decay emitting

an a-

particle

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Number of radioactive atoms

decreases by exponential decay

Image from: http://www.flickr.com/photos/mitopencourseware11


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Quantities used in radiation studies

Amount of radiation producing effect is specified as energydeposited per unit mass in irradiated material. This is

absorbed dose (D)

mD

Where

is energy absorbed in mass

m. This ismeasured as J/kg and SI unit is gray (Gy)

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However, each type deposits its energy in different way

Low-LET High-LET

-, -particles and neutrons and denselyionizing radiations.

The energy is distributed

inhomogeneously

X and -rays are sparsely ionizing radiationsEnergy is distributed homogeneously

Linear energy transfer (LET) is measure of energy transferred by ionizing

particle to traversed material. This measure is typically used to quantifyeffects of ionizing radiation on biological specimens and is usually

expressed in units of keV/m

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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 absorbed radiation dose (equivalentdose) - computed average measure of radiation

absorbed by fixed mass of biological tissue

accounts for different biological damage

potential of different types of ionizing radiationon different organs, considering differences in

their RBE

Equivalent dose is a judged quantity for

assessing health risk of radiation exposure

Equivalent Dose

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Equivalent dose cannot be measured directly. Dose for each tissue Tand each type of radiation R (often denoted by HT,R) is calculated by:

HT,R= Q x DT,R

where DT,Ris total energy of radiation absorbed in unit mass of tissue T,

and Q is radiation quality factor that depends on type and energy ofthat 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 raysabsorbed in one kilogram of tissue

Sv has replaced the previous unit rem (roentgen equivalent man):

100 rem = 1 Sv

Equivalent Dose

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Radiation quality or weighting factors

Radiation Type Energy W (ICRP-60) W (ICRP-92)

Photons all 1 1

Electrons,

muonsall 1 1

Neutrons 100 keV- 2Mev 20 function

Neutrons >2 -20 MeV 10 function

Neutrons >20Mev 5 function

Protons


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Chromosomal structure

Association of DNA andhistones in nucleosome

structure has been

demonstrated in

considerable detail. DNA isexternal to the histone core

of nucleosome. Some

studies support existence of

axial core structure formed

by non-histone proteins ornon-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 46chromosomes 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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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 ofwater

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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+ H3O

++ OH (3)+ H2O

H2O+ OH + H+ (4)

Electron becomes hydrated by water (5) and electronically excited watercan decompose into OH and H(6). So, three kinds of free radicals are

initially formed OH , H, and e-aq

+ H2Oe- (5)e- aq

H2O* (6)OH + H

Globally, and after further reactions, radiolysis of water in presence of

oxygen produces: OH, e- aq, H, O2

-, H2O2, H2.

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Low-LETradiation can

produce localized cluster of

ionizations within single

electron track

High-LETradiation produces

somewhat larger number of

ionizations that are closertogether

Damage in DNA

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Estimation of numbers of

radiation - induced

different types of DNA

lesions after 1 Gy

irradiation with low-LET

radiation

Types of DNA lesions

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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 likedicentrics.

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 G0phase and during cell cycle in G1but 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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module 1_basics of biological effects of ionizing radiation

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