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Radiation Biophysics

Radiation biophysics is concerned with the interaction of ionizing radiations with matter
and the effects on biological systems. Radiation in lower energy interacts with matter by
excitation processes but high energy radiation can ionize atoms and the liberated primary
electrons can further ionize or excite neighboring atoms.
The biological effects of radiation depend on the energy and the penetration power of the
incident radiations and the nature of the target. rays have less penetrating power
comparing to - rays and X-rays. But, rays have very high ionization power. Hence the
biological damage caused by rays are more compared to - rays and X-rays.
Ionizing Radiation
All radiations of the electromagnetic spectrum have similar characteristics, but differ
widely in their energies- from low energy radio and microwaves to infrared, visible and
ultraviolet light to high energy X-rays and - rays. Radiation biophysics, in general, is
concerned with the interaction of ionizing radiations (above 500eV), such as X-rays, rays, - rays, rays, protons and neutrons, with matter and the resulting damage to the
systems.
Excitation and Ionization
Interaction of radiation with matter can lead to either (i) excitation or (ii) ionization,
depending on the energy of the incident radiation. If the energy of the incident radiation
is below the threshold ionization potential, it can lead to excitation from one state to
another, as incident energy is not sufficient to knock out the electrons from the attractive
force of the nucleus of the atom. Excitation energies are in the UV region.
High energy radiations such as X-rays and - rays have sufficient and even excess kinetic
energy above the ionization threshold potential of atoms so that they can completely
remove electrons from the atoms, leading to ionization.
A A + eRadiation Sources
Sources of ionizing radiations are natural as well as manmade. Cosmic rays, radiations
emitted by radioactive decay, such as - particles, protons, neutrons and photon emission
are natural sources. The interaction of any radiation with matter depends on its energy,
penetration power and other characteristics specific to the radiation and to the target.
- rays
rays are high energy Helium nuclei released in the decay, that occurs in heavy
nuclei(generally Z> 83) with excess of protons and neutrons, such as thorium, uranium,
and radium.

The penetrating power of rays is very low- they can be stopped by a thin sheet of paper.
However, they have very high ionization power. The particles can cause considerable
radiation damage to skin tissues in organism, since all their energy is deposited in a very
high small tissue volume and is therefore radiotoxic.
- rays
- rays are high energy electrons produced by the transformation of neutrons into protons
with emission of electrons. Transformation of protons into neutrons induces the emission
of positrons.
Neutron Proton + Electron + Antineutrino
Proton Neutron + Positron + Neutrino
Interaction of high energy - rays with matter results in excitation, ionization and
Bremsstrahlung processes. The penetration of - rays, which is about ~1cm in biological
tissues, is higher than that of rays.
Protons and Neutrons
Protons are hydrogen nuclei. Neutrons transfer their kinetic energy through elastic,
inelastic and particle capture processes. In the inelastic collision process with an atomic
nucleus, part of the kinetic energy is utilized to excite the nucleus and the excited nucleus
emits radiation. Neutrons do not produce ionization directly, but indirectly by ejecting
protons of the atomic nuclei of the target material. In effect, the biological effects of
neutrons are due to the protons they produce.
X-rays and - rays
Both X-rays and - rays are high energy photons, irrespective of their mode of
production, and their effects on biological systems are quite similar. While X-rays are
produced due to atomic transitions of core electrons on bombardment of any heavy
element target by high speed electrons, - rays are produced in nuclear reactions,
whenever there is a transition of a nucleus to the ground state or by annihilation of an
electron-positron pair.
Interaction of Radiation with Matter
There are 3 processes by which high energy radiations interacts with matter.
1) Photo-electric effect
2) Compton effect

3) Electron- positron pair production


Photoelectric effect
At lower energies (<30KeV) the photoelectric effect comes into operation. In this process
all the energy of the incident radiation is used in ejecting a bound electron resulting in
ionization. The electrons thus produced are called photoelectrons. Photoelectrons are
absorbed locally, causing ionization and excitation. The photoelectric effect is
predominant at lower energies (<0.1 MeV) and for elements of high atomic numbers.
Compton effect
At medium energies (<10MeV) the Compton effect is dominant. The Compton effect is
inelastic scattering, where the incident photon transfers part of its energy to a weakly
bound electron. This electron is called recoil electron. As a result of the energy transfer
during collision the photon will have a reduced energy. The Compton effect is prominent
at moderately high energies and for materials of low atomic number.
Pair Production
Radiations (photons) with energies > 1.02Mev in the presence of a nucleus of an atom
will split up into an electron and positron (a particle and its anti particle). The presence of
nucleus is essential for the conservation of angular momentum. This process is called pair
production.
Beer- Lambert Law
The radiation passing through matter is attenuated due to absorption and scattering.
Attenuation due to absorption follows the Beer-Lambert law
I = I0 exp (- x)
I transmitted intensity
I0 incident intensity
linear attenuation coefficient
x thickness of the material (target)
The linear attenuation coefficient of the material is related to its atomic number and,
therefore, the mass attenuation coefficient m is dependent on density, , given by,
m = /
The total attenuation is the sum of 3 components due to 3 processes- photoelectric ( p),
Compton (c), and pair production ().
i.e. total = p + c +
Dosimetry- Measurement of radiation

Dosimetry deals with the various methods of radiation measurements, both physical and
chemical.
Absorbed Dose (D)
Absorbed dose, D, is the energy absorbed by unit mass of the material.
D = Energy imparted / Mass
The unit of absorbed dose is Grey.
Gy = 1 J/kg

Dose equivalent
Radiation induced biological effects also depends on the type of radiation and the nature
of the target etc.
Dose equivalent, is the absorbed dose, weighted according to the damage potential of the
incident radiation. The unit of Dose equivalent is Sievert, Sv.
Effective Dose Equivalent
Not all parts of the organisms are equally sensitive to a given radiation. So, different parts
of the body should be given appropriate weightage.
Radiation dose is measured by various methods- by physical Dosimetry that includes
ionization chambers, GM counters, luminescence and photographic methods and by
Chemical Dosimetry.
Physical Dosimetry
High energy radiations can be measured with gas filled scintillation and semiconductor
detectors. The measurement of the number of ionizations is the basic principle on which
physical Dosimetry is based. Dosimetry of photon radiation is carried out by methods
based on ionization of air. A closed chamber is filled with an inert gas and is subjected to
steady ionizing radiations which will produce a fixed number of ions per second.
Photon detectors are good for measuring lower energy range radiations and electron
detectors are more useful in higher energy radiation regions, where secondary electrons
play a prominent role in causing biological effects.
In all these detectors, the amplitude of the pulse is non-linearly related to the applied
voltage and detecting devices perform with maximum efficiency in their appropriate
voltage regions (ex. GM counters have maximum efficiency in their operating region).
The ionization chambers one of the most commonly used radiation detectors. In any
ionization chamber device there is a closed chamber containing air or inert gas and the
electric field is applied between the two electrodes. There are 3 distinct regions of the
operation of the counter

1) Ionization region
2) Proportional counter region
3) Geiger region
In the ionization region (<300V), ionization of the gas in the chamber caused by high
energy radiation is proportional to the incident radiation.
In the proportional counter region, the applied voltage is above the ionization level but
below the Geiger voltage. In this region the number of the electrons reaching the anode
increases rapidly with the applied voltage, due to the formation of secondary ion pairs.
But, the pulse amplitude is still proportional to the initial ionization and the total number
of the secondary electrons is proportional to the number of primary ion-pairs produced by
the original ionizing radiation. Detectors operating under these conditions are called
proportional counters. They are ideal for counting high counting rates and are essential
for the detection of particles of high ionizing power, such as particles.
In the Geiger region the applied voltage is higher than the proportional counter voltage.
In a GM counter, a high potential is applied to the central anode ire which is surrounded
by a cylindrical cathode. The tube is filled with a gas mixture (ethane + argon) and is
sealed. A thin mica or glass window acts as an entry area for incident radiation. An
incident ionizing particle initiates ion-pair production in the GM tube. These ion-pairs
collide with neighboring gas molecules and ionize them. Such cascade collisions of ions
produce an avalanche of ionization, and the electrons upon reaching the anode produce
photons which in turn produce ionization. Geiger counters are simple, rugged and easy to
operate but sluggish. They are used for the detection and monitoring of high energy
radiation and - particles.
Semiconductor detectors are also used in physical Dosimetry.
Scintillation counters
The fluorescent effect, that is, the conversion of high energy radiation into a visible
spectrum by chemicals, is measured by scintillation counters. Almost all nuclear detectors
employed in nuclear medicine utilize scintillation technique.
Silver activated zinc sulphide is a good scintillator for particles and for counting - rays
sodium iodide doped with thallium iodide is generally employed.
There are 2 types of scintillation counters- solid scintillation counter and liquid
scintillation counter.
In liquid scintillation, the scintillation solution consists of solvents such as benzene,
toluene, etc and solutes such as naphthalene, Carbazole etc.The solvent acts as a medium
for absorbing the energy from the ionizing radiations. This results in the formation of
excited solvent molecules, which will eventually transfer energy to the solute molecules,
which acts as a source of photons.

High energy charged particles (such as electrons) traveling with a velocity, v, through a
medium of refractive index, n, radiate a part of their energy if their velocity, v, is above
the threshold.
V > C / n.
Where C velocity of light
This radiation is called Cerenkov radiation.
Chemiluminescence and Bioluminescence
Chemiluminescence and bioluminescence result from internal reactions in a solution
leading to products in excited states.
A + B C* + D
C* C + h
The degree of darkening of a photographic emulsion due to radiation is the basis of the
photochemical measuring devices such as photographic plates, film etc.
Chemical Dosimetry
Oxidation of ferrous to ferric ions (Fe2+ Fe3+ ) by the products of radiolysis of water is
a convenient method of chemical Dosimetry. This is the basic principle of the Frickes
dosimeter. The Frickes dosimeter has a dilute solution of a mixture of ferrous
ammoniumsulphate and NaCl and H2SO4. The reaction is carried out at pH = 1.5.
Radioactive Isotopes
Another common source of ionizing radiation is radioactive isotopes. Radioactive
isotopes (radio nuclides) are of considerable importance in the diagnostics of radiation
effects on biological systems as well as therapeutic purposes in nuclear medicine.
Radioactivity
Certain atomic nuclei (radio nuclides) which are unstable achieve stability by radioactive
decay, giving rise to other types of isotopes and atoms. The - decay processes transform
neutrons to protons and protons to neutrons with the emission of electrons and positrons
respectively. The decay process emits particles and transition of the excited nuclide to
ground state causes the emission of photon.
The rate of radio active decay can be expressed by Poissons distribution and is
characteristic of that nuclide and is independent of physical and chemical environments.
The rate of decay is given by
N = N0 exp (-t)
Where N0 number of radioactive atoms at the initial time (t=0)
N number at time t
decay constant
The period during which the radioactive decay of a radionuclide is half of its initial value
is called half-life ().

= 0.693 /
Average life time, T= 1/
The amount of radioactivity, A, ( A=N), is measured in terms of disintegration rate.
The unit is Becquerrel, Bq.
1 Bq = 1 disintegration/ second
1 Bq = (1/3.7) x 10-10 Curie.
Production of Radio nuclides
Radio nuclides are isotopes (elements with same atomic number but different mass
numbers) that reach stability by emitting radiation or particles. A radio nuclide is
characterized by its half-life, type of decay and the type of particle emission and its
energy. The most important method of producing artificial radio nuclides is by neutron
bombardment of a required material in an atomic reactor. The transformation is denoted
by
A (, X) B
Where A initial nucleus
B final nucleus
bombarding particle
X emitted particle (radiation)
Application of Radioactive Tracers
Radioactive labeling has extensive applications in biological & clinical fields in many
assay methods and in monitoring of chemical reactions.
1) Radioimmunoassay (RIA)
One of the important applications of radioactive tracers is the Radioimmunoassay (RIA)
method. This method can be employed to assay substance present in small quantities with
a high degree of specificity and can be used in the diagnostic monitoring of abnormalities
of body functions, enzyme catalysis and other biochemical reactions.
RIA is based on the high degree of affinity of an antibody for specific antigens. The
general principle of RIA is the quantitative measurement of the ratio of labeled antigen
(Ag*) molecules to an unknown quantity of assay antigen, Ag (that is present in the
sample) competing for the binding sites of a known quantity of an antibody (Ab).
In RIA a known quantity of labeled antigen (Ag*) is added to a known quantity of
antibody (Ab)(in addition to the unlabelled antigen, Ag).
When there is an excess of antigen molecule (Ag and Ag*) for a known quantity of
antibody, Ab, there arises a competition of Ag with Ag* for the same sites of the antibody,
Ab. At equilibrium,

Ag + Ab Ag . Ab

Ag* + Ab Ag*. Ab
In this reaction, increase of Ag leads to decrease in Ag*. Ab complex (therefore decrease
in its radioactive counts). The assay is based on the quantitative evaluation of the total
labeled antigen, Ag*, bound to the antibody (Ag*.Ab complex) from the radioactive
counts of the free and bound ligands from which the amount of unlabelled (Ag) can be
calculated.
At equilibrium, the ratio of the antigen in the bound state (F) and free (F) phase is
B/F= [Ag.Ab]/ [Ag]
A dose-response plot of F/B versus the antigen concentration is a hyperbolic curve and
the reciprocal of the receptor concentration can be calculated from the slope of the curve.
In RIA, the selection of the radiolabel is determined by the structural and sensitivity
requirements of the immuno response system. 131I or 125I is the generally employed radio
label. Once the equilibrium state is reached the components are separated. This can be
carried out by several methods such as- Chromatophoresis, gel filtration, salt
precipitation etc. The choice of the counting system depends on the type of isotope used
for labeling.
2) Autoradiography
Radioactive tracers are employed in autoradiography. It is a record of the traces of
ionizing radiations emitted by the radioactive compound on a photographic emulsion.
This technique is very similar to the detection of the paths of high energy particles
photographically. In biological studies, alpha particles and gamma rays are not employed.
Beta emitters such as 3H, 32P and 35S isotopes are generally preferred.
The degree of darkening of exposed photographic emulsion is a measure of the amount of
radio active substance present.
Various variations of the general technique, such as micro-, macro-, and electron
microscope autoradiography are in use to cater to different requirements. In macro- as
well as in micro-autoradiography, the organisms or their parts are placed in contact with a
photographic emulsion to produce an autoradiograph. Electron microscope
autoradiography is employed to achieve higher resolution than possible with light
microscopy.

Biological Effects of Radiation

Dose Response Relationships


Biological radiation data are analyzed by dose response relationship graphs. The end
result of the dose-response is the result of many intermediary reactions. For chemical
reactions where the radiation process is indirect, the relationship between dose and the
observed chemical change depends upon the reaction product. If the product does not
interact with free radicals, then the number of molecules damaged is directly proportional
to the dose applied.
Target Theory
The dose-response relationship is explained by the target theory, which is based on the
assumption that within a cell a target has to be hit directly to induce cell damage. The
radiation damage can either be due to single-hit dose or multi-hit dose response. The
dose-response relationship for a single hit dose is semi-logarithmic and the surviving
fraction, S, is
S = Ns/No = e-D
where No is the no. of targets exposed and Ns is the number surviving after irradiation and
is the inactivation coefficient, which depends on the volume of the target, dose-rate etc.
The inactivation coefficient of the single hit dose-response relationship represents
irreversible radiation damage and does not take into account other factors such as belowlethal damage and cellular repair processes. The DNA is taken as the principal target for
radiation damage.
Dose-response curve which are sigmoid in shape are due to multi-hit processes combined
with molecular repair processes. An end-effect can be due to a combination of single hit
and multi hit. In multi-hit processes, the damage is dose-rate dependent at higher doses.
Radiolysis of Water
In biological systems, water is abundant. Its high affinity for electrons makes the
radiolysis of water a primary event in the initiation of primary damage in the living cells.
Absorption of radiation by water leads to ionized species which further react with
neighboring water molecules or other polar molecules, to form a variety of new reactive
species. Free radicals are not the primary products of the radiolysis of water, but
secondary products from subsequent decomposition of ions and excited species produced
initially.
h
H2O ionisation

H2O+ + e-

H2O H+ + OHH2O OH+ + H + e-

H2O+ + e- H2O*
H2O+

H+ + OH

H + OH+

H2O* H + OH

H2O + e- H + OHH2O+ + H2O H3O+ + OH-

Hydrolysis of free radicals, OH , which are very reactive can form hydrogen peroxide,
which is a powerful oxidant.

OH + OH H2O2
Free radicals and H2O2 can react with the body system and can cause various kinds of
damage including cancer.
The role of oxygen
Oxygen is a highly reactive molecule. In the presence of oxygen the reactions produced
by ionizing radiations are different and are more harmful biologically. In the absence of

oxygen, radicals R and X can react with one another or dimerise, Rn.

R + X
or

RX

R + R + R .... Rn

Presence of oxygen blocks restoration processes and enhances radiation damage. In the

presence of oxygen, the formation of the peroxy-radical, RO 2 , is the predominant


reaction

R + O2

RO2

Peroxy radicals cannot dimerise or polymerise but give rise to hydroperoxide.

RO2 + H RO2H

Irradiated water containing dissolved oxygen leads to the formation of relatively large

amounts of perhydroxy radicals (HO2 ). Therefore, all biological systems are more
radiosensitive in the presence of oxygen.

H2O + O2 HO2 + OH2


Each perhydroxy radical can oxidize 3 molecules.

3RH + HO2

3R

+ H2O

Therefore, a dose of radiation is more destructive to a biological system in the presence


of oxygen than its absence.
Effects of Radiation on Living Systems
Ionising radiations can break the chemical bonds and radically alter the chemical
structures of biological molecules. The principal reaction of the amino acids in aqueous
media is deamination with the release of water. Free radicals, produced on radiolysis of
water, can react with macromolecules and damage them. Presence of oxygen enhances
the damage. Almost all proteins are denatured by ionisation which results in the lose of
enzyme activity.
Radiation damage to the genetic material can be hereditary or somatic. Radiations can
directly damage the chromosomes, considered to be the root cause of the cell damage. A
mutated cell may transmit flowed genetic message via its DNA to other cell generations.
Radiation may cause cell division not to occur at a proper time. Therefore, acute damage
is most likely to occur in those cells which are undergoing rapid cell divisions.
Consequently, infants are more susceptible to radiation damage than adults. Radiation can
also cause opaqueness and cataract in the eye.
Radiation carcinogenesis is a stochastic process. In general carcinogenesis takes place in
2 steps- initiation (irreversible) and promotion. Ionising radiation acts as initiator as well
as promoter. Carcinogenesis may occur mainly as a result of acute (short time span) doses
from atomic weapons or therapy.
All forms of ionising radiations are harmful above certain minimum dose levels.
Exposure to ionising radiations cannot be completely avoided as human beings are
exposed to these from natural as well as manmade sources of radiation. The mst
important natural sources of radiation are the decay products of radon, 222Rn. 222Rn is the
gaseous daughter product of radium, 226Ra. 222Rn is released into the atmosphere due to
uranium, building construction etc.
On inhalation of radon gas, the decay products are absorbed as aerosol particles by the
bronchial tissues, leading to lung tissue damage and lung cancer.
Other naturally occurring nuclides are 42K, 90Sr, and 131I being gaseous can spread over a
large area and is absorbed by living organisms through the food chain. It causes minimal

damage due to its very short life time. Of all machine produced sources, medical X-rays,
gamma rays in nuclear medicine and in nuclear reactors constitute high health hazards.
Accumulated low doses can start off chain reactions leading to genetic damage and
cancer. A dose of 0.25Gy is considered as the limiting dose. Dosses in the range below
1Gy affect sensitive organs and tissues, such as bone marrow tissues. Doses 1Gy
damage eyes leading to blindness, cause deficiencies in the immune system and leads to
anaemia. Doses in the range of 3-5Gy lead to death in few months due to bone marrow
damage, haemorrhages, anaemia, infection and malnutrition. Doses of 10-40Gy lead to
death within weeks & very high doses, >100Gy cause death within hours or days due to
the damage of central nervous system.
Radiation Protection and Therapy
Radiation Protection
As radiolysis of water produces free radicals, addition of substances that complete for
these free radicals could minimize the random effect. Some of the molecules rendering
chemical protection against radiation are cysteine and molecules containing free
sulphydryl (-SH) groups and chelating agents such as EDTA.
Charge delocalization reduces the no. of radicals produced at the target, by diffusing them
to wider areas. Therefore, aromatic agents are better protectors in charge-transfer
mechanism. Macromolecules such as proteins can be protected by competitive removal of
radicals or repair through a hydrogen-transfer reaction.
PH + OH* P* + H2O
P* + XH PH + X*
Where P is a polymer, P* is the polymer radical and XH is the protective reagent.
Colloidal sulphur is a protecting agent for enzymes.
Protective of sensitive organs and sites from irradiation is another method of protection.
As longer wavelength X-rays are absorbed by the skin surface leading to skin damage,
filtering of such radiations can be achieved by shields (Al, Cu etc).
Radiation Therapy
In spite of the hazardous nature of ionizing radiations, living organisms have to live with
them and they are very much part of nuclear medicine for diagnostic as well as
therapeutic treatments. X-rays are used in Roentgenography and CAT-scan radiography.
Radioactive isotopes are employed as tracers in many biological processes. Labeled radio
nuclides can easily be monitored due to their radioactivity and high sensitivity. Various
functions of organs and their abnormalities can be monitored by such methods. Some of
these include diagnostics of the function of the thyroid gland by radio iodine, the function
of kidneys by renography etc.

Labeled proteins are used in clinical investigations. By such investigations any


abnormalities due to the effects of radiation or chemicals can be evaluated.
Tumors (rapidly dividing cells with undifferentiated structure) are more sensitive to
radiation than strongly differentiated cells undergoing cell slow division. Use of ionizing
radiation in cancer therapy is based on the sensitivity of different types of cells to these
radiations. Present day radiation therapy relies on the administration of radiation dose not
in a single shot but in fractions separated over time period. This procedure is to allow the
recovery of normal calls from the effects of radiation.
Problems
1.

The half-life of radioactive substance is 48 hr. How much time it will take to disintegrate to
its 1/16th part.
Solution:

2.

Carbon-14 is one of the isotopes of carbon with a half life of 5,730 years. Find the
decay
constant
()
for
this
element.
Solution: We know the half life of C-14, from which we are expected to compute its
decay constant. The equation that connects these two quantities is:
t1/2

ln

Therefore,

rearranging

0.693

terms,

we

get:

= ln 2 / t1/2 = 0.693 / t1/2 = 0.693 / (5730 x 365 x 24 x 60 x 60) sec = 3.836 x 10 -12
per
second.
So the decay constant of Carbon-14 is 3.836 x 10-12 per second.

3.

Cobalt-60 has a half life of 5.27 years. Find the average life time of each cobalt-60
atom.
Solution: The half life of Co-60 is given to be 5.27 years. To find the average lifetime
() of one cobalt-60 atom, the following formula must be used.

but

we

Therefore

know
the

that,

above

0.693
equation

t 1/2
becomes,

= t1/2 / 0.693 = (Half life of C0-60) / 0.693 = (5.72 x 365 x 24 x 60 x 60 sec)/ 0.693
=
8.25
years
Thus, the average life time of any cobalt-60 atom is 8.25 years.
4.

The half-life of radium-226 is 1600 years. Suppose you have a 22mg sample.
After
how
long
will
only
18mg
of
the
sample
remain?
Solution:
= 0.693 / t1/2

1600=(0.693
=(0.693)/1600

N=N0exp(
18=22
t=
t = 463.211 years

=~-0.000433216988
-t)

e
~463.210587512

-0.000433216988*t

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