biological effects of ionizing radiation_laura j
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Biological effects of
ionizing radiation
Laura Jiménez Hernández
Universidad Complutense de Madrid
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Abstract
The aim of this paper is to investigate what occurs in biological matter when it is
exposed to an ionizing radiation. We will first see how different kinds of radiations
interact with the atoms that compose the tissue’s matter, to study later the effects at a
chemical stage in order to understand finally the biological effects. We will study the
classification of these effects depending on factors as the spanned time between the
radiation exposure and the manifestation of the biological effect. Finally we will
inspect some radiation protection methods
1. Introduction
Radiation is energy transmitted through space in the form of electromagnetic waves or
energetic particles. When the radiation has sufficient energy, it can remove electrons
from atoms in the material trough which it passes. This process is called ionization, and
the high frequency electromagnetic waves that can produce it are called ionizing
radiations. In this group we can include: alpha particle radiation, beta particle
radiation, neutrons, gamma rays, and X-rays
Most of this electrons removed by ionizing radiation are produced with energies in therange 10-70 eV
Non-ionizing radiations are not energetic enough to ionize atoms and interact with
materials in ways that create different hazards than ionizing radiation. Examples of
non-ionizing radiation include: microwaves, visible light ,radio waves, ultraviolet
lights…
Lives on Earth have always been exposed to a certain level of natural radiation: cosmic
rays, radioactive materials found in the earth’s crust, in the air, or in the food; and
even radioactive substances inside the human body (potassium, carbon…)
Apart from this natural sources, the men has developed artificial ionization radiations
as X-ray machines
Early human evidence of harmful effects as a result of exposure to radiation in large
amounts exists since the 1920s and 1930s, based upon the experience of early
radiologists, miners exposed to airborne radioactivity underground, persons working in
the radium industry, and other special occupational groups.
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We will investigate in this paper how the excitations and ionizations produced by the
radiation can interact with the living matter breaking chemical bonds, producing free
radicals and damaging molecules that regulate vital cell processes (e.g. DNA, RNA,
proteins)
2. Previous concepts about radiation dosimetry
Radiation dosimetry attempts to relate specific measurements of radiation fields to
chemical or biological changes produced in a target. Dosimetry is essential for
quantifying the various biological changes as a function of the amount of radiation
received, the dose-effect relationship
In this block we will see the most common units and parameters used in radiation
dosimetry to understand better the results that we will after expose along this paper
Exposure
It is a measure of the ionizations of the molecules in a mass of air. The main advantage
of this unit is that it is easy to measure directly, but it is limited because it is only for
deposition in air, and only for gamma and x rays. The unit used for this measurement is
the Roetgen (R). One Roentgen is equal depositing to 2.58 x10 coulombs per kg of
dry air.
1 R = 2.58 x 10C/kg
Absorved dose
Throughout this paper we will use the SI unit called gray (Gy) to relate to the amount
of energy absorbed in a certain material . One gray is equal to one joule of energy
deposited in one kg of a material:
1 =1
=
10
10= 10
= 100
There is another important unit r related to the absorbed dose: the RAD (Radiation
Absorbed Dose). One rad is defined as the absorption of 100 ergs per gram of material
1 rad = 100 ergs/g
Relative biological effectiveness (RBE)
There is a difference on the density of ionization depending on the radiationimplicated: neutrons, protons, and alpha particles produce more biological effects per
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unit of absorbed radiatio
rays, gamma rays, or elec
parameter RBE
The relative biological eff
the dose of a reference
biological effect as was see
Different values of RBE mothers:
Let’s note that radiation o
important to remember h
fully absorbed within the f
of the radiation is extern
layers of dead cells. But if
radiation energy will be
surrounding each particle.
dose than do more sparsely ionizing radi
rons . To take into account these differenc
ctiveness (RBE) for a given test radiation,
radiation, usually x rays, required to pr
n with a test dose, DT, of another radiation:
BE =Dose from reference radiation
Dose from test radiation, DT
ean that certain types of radiation are mo
Table 1: Relative biologic
Source: UW Environme
f Alpha particles is referred to radiation int
ere that the energy of these positively cha
irst 20 micrometers of an exposed tissue m
l, all of the alpha radiation is absorbed i
the If alpha emitting material is internally d
absorbed in a very small volume of tiss
4
tions such as x
es it is used the
is calculated as
duce the same
re harmful than
al effectiveness-
tal Health and Safety
o the body. It’s
rged particles is
ss. If the source
the superficial
eposited, all the
ue immediately
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Linear energy transfer (L)
“Linear energy transfer (L) of charged particles in a medium is the quotient of dE/dl,
where dE is the average energy locally imparted to the medium by a charged particle
of specific energy traversing a distance of dl.” ICRU, 1962. LET is generally expressed in
units of keV/μm
L = dE/dl
It’s clear that different radiations will have different effects in the materials, and thus
in the biological tissues. In the following table we can see some characteristics of
ionizing radiation with a kinetic energy of 1 MeV. For the same energy, the heavier
particles are slower, stopped easier and deposit their entire energy over a shorter
distance
Alpha Proton Beta Photon(X
ray)
Neutron
Charge +2 +1 -1 neutral neutral
Ionization Direct Directs Direct Indirect Indirect
Mass(amu) 4.0015 1.00727 0.0005485 - 1.008665
Velocity(cm/sec) 6.94× 10 1.38× 10 2.82× 10 c 1.38× 10
Table 2: Comparison of Ionizing Radiation
3-Chemical Interactions
To understand the effects of radiations, one must first be familiar with their interaction
mechanisms
The transfer of energy from photons to tissue takes place into two stages: First, theinteraction of the photon with an atom, causing an electron to be set in motion, and
second, the subsequent absorption by the medium of the kinetic energy from the high
energy electron
There are three ways in which the photon can interact with the atoms, and thus
promote the ionization:
- Photoelectric effect: One electron from the atom is pulled and it takes the
energy from the incident photon
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- Compton effect: An inelastic collision between the photon and the electron in
the atom
- Pairs production- This is the dominant phenomena when we are talking about
high energy photons . The photon disappears and an electron–positron pair is
formed. Since the rest mass energy of an electron/positron is 0.511MeV, pair
production requires a photon of at least 1.02 MeV to occur.
After the electron produced by a photon interaction passes through tissues, exciting
and ionizing atoms and molecules. A number of important chemical events that
precede the biological effects take place
Mammalian cells are typically 70-85% water, 10-25% proteins, 10% carbohydrates and
2-3% lipids
When the electron that was shared by the two atoms to form a molecular bond is
dislodged by ionizing radiation, the bond is broken and thus, the molecule falls apart.
The ionization of the water molecule can be written as:
→ +
The ion reacts with another water molecule to form the highly reactive hydroxyl
radical:
+ → +
The excited water molecule can also get rid of its energy by molecular dissociation:
→ +
→ +
The vibrational periods of the water molecule are ~10, which is the time that
characterizes the dissociation process
At 10 after passage of a charged particle in water, there have been produced four
chemically active species ,, and H
Between these reactants there are three free radicals:, and H, that is, chemical
species with unpaired electrons. These free radicals are highly reactive chemically and
can themselves alter molecules in the cell
The reactants begin to migrate randomly about their initial positions in thermal
motion. As their diffusion in water proceeds, individual pairs can come close enough to
react chemically
Radicals are highly reactive and thereby able to damage all macromolecules, including
lipids, proteins and nucleic acids.
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One of the best known
membranes (plasma, mito
a process known as lipid p
We can summarize the pro
To summarize ,we can co
cell: direct and indirect ac
radiation itself and indire
radicals and other radiatio
DNA caused by an ionizati
stand break that results w
4.1 Type of effects
The biological effects o
characteristics of effects, o
Deterministic effects
It was discovered that se
increasing doses. There ex
will be absent. This kind of
toxic effects of oxygen radicals is da
hondrial and endomembrane systems), whi
roxidation.
cess of the indirect effects in this sketch:
sider two different ways in which the radia
ion. Direct effects are produced by the ini
ct effects are caused by the later chemic
n products. An example of a direct effect is
n in the molecule itself. An indirect effect is
en an OH radical attacks a DNA sugar at lat
4-Biological effects
f ionizing radiation can be classified ac
ccurring times and the object that shows th
erity of certain effects on human beings w
ists a certain level, the "threshold", below
effects is called "deterministic effects".
7
age to cellular
ch is initiated by
tion acts on the
ial action of the
l action of free
a stand break in
for example the
r time
cording to the
effects.
ill increase with
hich the effect
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For any biologically harmful agent, it is useful to correlate the dosage administered
with the response of damage produced, in order to establish acceptable levels of
exposure. This is what we call “the dose response curve”
Figure 1 represents the dose response curve for a deterministic effect. It is a typical
“threshold” curve. The point at which the curve intersects the abscissa is the threshold
dose, i.e., the dose below which there is no response
Skin reddening is an example of a deterministic effect of radiation
Stochastic effects
The severity of stochastic effects is independent of the absorbed dose. Under certain
exposure conditions, the effects may or may not occur. There is no threshold and the
probability of having the effects is proportional to the dose absorbed.
Figure 2 represents a linear, non-threshold relationship, in which the curve intersects
the abscissa at the origin. Here it is assumed that any dose, no matter how small,
involves some degree of response. There is some evidence that the genetic effects of
radiation constitute a non-threshold phenomenon
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Stochastic effects occur in a statistical manner. Cancer is one example. If a large
population is exposed to a significant amount of a carcinogen, such as radiation, then
an elevated incidence of cancer can be expected
Depending on the dose, kind of radiation, and observed endpoint, the biological
effects of radiation can differ widely. Those effects which appear within a matter of
minutes, days, or weeks are called short-term effects and those which appear years,
decades, and sometimes generations later are called long-term effects.
4.1.1 -Short term effects and the acute radiation syndrome
A radiation which is delivered to the body during a very short time is what we call an
acute dose of radiation. If a person receives a single, long, short term dose of radiationa number of vital tissues and organs can be damaged
The latent period or time elapsed between the radiation insult and the onset of
effects, is relatively short and grows progressively shorter as the dose level is raised.
The signs and symptoms which result from large doses of radiation, delivered to a
major portion of the body are known as “Acute Radiation Syndrome”
The acute radiation syndrome can be characterized by four sequential stages. The
initial phase is called Prodrome. It is usually characterized by nausea; vomiting and
malaise .It lasts until about 48 h after the exposure.
The second stage is called “latent”, and is characterized by a general feeling of well
being. Changes, however, may be taking place within the blood-forming organs and
elsewhere which will subsequently give rise to the next aspect of the syndrome. In the
next stage a number of symptoms develop within a short time. Damage to the
radiosensitive hematologic system will be evident through hemorrhaging and
infection. Other possible signs and symptoms are loss of hair (epilation), fever, severe
diarrhea, prostration, disorientation, and cardiovascular collapse
4.1.2- Long term effects
Some biological effects may take a long time to develop and become evident. The
latent period is much longer than the one we had in the acute radiation syndrome.
Delayed radiation effects may result from previous acute, high-dose exposures or from
chronic low-level exposures over a period of years.
Human studies of long-term radiation effects need a large number of people and the
employment of biostatistical and epidemiologic methodology
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The study is hampered by the fact that most diseases are probably “caused” by the
simultaneous interaction of several factors, and that the presence of some of these
factors without the others may not be sufficient to induce the disease
It is easier to work with animal populations, in which all factors with the exception of
radiation exposure are kept identical in study populations
Among the long-term effects thus far observed have been somatic damage, which may
result in an increased incidence of cancer, embryological defects, cataracts, and
genetic mutations, which may have an adverse effect for generations after the original
radiation damage.
A- Carcinogenic Effects
Ionizing radiation may be shown to exert an almost universal carcinogenic action,
resulting in tumors in a great variety of organs and tissues
Lung cancer is a good example. It was highly prevalent among the miners as a result of
the inhalation of large quantities of airborne radioactive materials. It was estimated
that the risk of lung cancer in the pitchblende miners was at least 50 percent higher
than that of the general population.
Radiogenic cancers are not distinguishable from others. Cancer risks at low doses can
only be estimated by extrapolating from human data at high doses where excess
incidence of cancer is evident
Different explanations have been purposed in the investigation concerning the
carcinogenic action of radiation
1- Activation of a Latent Carcinogenic Virus
The production of cancers is sometimes explained by the action of a virus which
attacks normal cells injecting itself into the cell nucleus. The genetic material of the
virus stimulates cells have a natural mechanism whereby the action of these virus is
resisted (when the virus is already in the cell) , it is the cell to reproduce wildly. If
normal possible that radiation and other carcinogenic agents may act as catalytic
agents, interfering with the cell resistance
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2- Damage of Chromosomes
Leukemia and other diseases have been associated with chromosome aberrations,
which van be a consequence of radiation damage
3- Mutations in Somatic Cells
Radiation can produce mutations in many kinds of cells in the body. It can affect to the
cells in the reproductive organs (germ cells) as well as those in other parts of the body
(somatic cells).
Somatic mutations probably occur constantly at a low rate in all organisms. Radiation
may accelerate the rate at which these mutations occur, and the resultant damage
accumulates gradually in the affected tissues.
4- Formation of free radicals
As a result of the irradiation of water molecules, which are abundant in all living cells,
certain short-lived but potent damaging agents called “free radicals” are formed and
may play an important role in both cancer and aging.
It’s very interesting to relate now our study of the carcinogenic effects with the
statistics of cancer risk among atomic-bomb survivors
The Life Span Study (LSS) cohort consists of about 120,000 survivors of the atomicbombings in Hiroshima and Nagasaki, Japan, in 1945 who have been studied by the
Radiation Effects Research Foundation (RERF) and its predecessor, the Atomic Bomb
Casualty Commission.
The LSS cohort of A-bomb survivors serves as the single most important source of data
for evaluating risks of low-linear energy transfer radiation at low and moderate doses
For the average radiation exposure of survivors within 2,500 meters (about 0.2 Gy),
the increase of solid cancer rates is about 10% above normal age-specific rates. For a
dose of 1.0 Gy, the corresponding cancer excess is about 50% (relative risk = 1.5).
The dose-response relationship appears to be linear, without any apparent threshold
below which effects may not occur
In Figure 3 The thick solid line represents the fitted linear sex-averaged excess relative
risk (ERR) dose response at age 70 after exposure at age 30. The thick dashed line is a
non-parametric smoothed estimate of the dose category-specific risks and the thin
dashed lines are one standard error above and below this smoothed estimate
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Figure 3. The dose-response relationship Source: Radiation Effects Research Foundation
The results represented in figure 4 show that higher risks are associated with younger
age at exposure. The right panel represents effects of age at exposure and attained
age on the excess relative risk of solid cancer (incidence) following exposure to 1 Gy.
The left panel represents instead the excess absolute risk
Figure 4- Attained age VS Risk. Source- Radiation Effects Research Foundation
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B- Genetic effects
The mutagenic property o
The most extensive studie
carried out with mice by
mutation rates under a var
One of the living things in
studied is the fruit fly (Dr
mutation resulting from on
Studies of genetic effects
radiation alters the geneti
ovum), the alteration can
Radiation-induced geneti
chromosome alterations.
The DNA is a macromolecuHydrogen bonded in pairs
bases in the DNA encodes
This molecule can be alt
mutation is called a point
Some mutations can also i
chromosomes can rejoin
arrangement. Chromosom
Picture 1: Normal
Drosophila male and
drosophila male with
four wings. Source:
National Academy of
Science
ionizing radiation was discovered by Muller
of the genetic effects of radiation on ma
.L.Russell and L.B. Rusell. They investigat
iety of conditions of dose, dose rate, and do
which morphological mutations have been
sophila melanogaster). In Picture 1 we ca
e spontaneous and two X-ray induced muta
in humans are most complicated. It’s kn
c information contained in a germ cell or
e transmitted to future generations
changes can result from gene mutat
he first one occurs when the DNA is altered.
le whose structure is a linear array of four vinto a double-helical structure. The partic
he entire genetic information for an individ
red even by a loss or substituition of a
mutation when there is a change at a si
nvolve a deletion of a portion of the chro
in various ways, introducing errors in
aberrations occur in somatic cells
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in 1927.
mals have been
d specific locus
se fractionation
most intensively
appreciate the
tions in this fly:
own that if the
ygote (fertilized
ions and from
arieties of basis.lar sequence of
al
ingle base. The
gle gene locus.
osome. Broken
to the normal
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Most geneticists agree that the great preponderance of genetic mutations are harmful.
By virtue of their damaging effects, they can be gradually eliminated from population
by natural means, since individuals afflicted with this damage are less likely to
reproduce themselves successfully than normal individuals.
C- Embryological Effects
Considering the fact that immature and rapidly dividing cells are highly sensitive to
radiation, it is not surprising that embryonic and fetal tissues are readily damaged by
relatively low doses of radiation.
The principal effects of in-utero irradiation are prenatal death, growth retardation and
congenital malformations
The degree of the effects varies with the stage of development at the time of
irradiation. We can identify three stages:
1. Preimplantation. The time between fertilization of the egg and its implantation
in the uterine lining
2. Maximum organogenesis: The time during maximal formation of new organs
3. Fetal. This is the final stage, with growth of performed organs
The unborn is considerably more sensitive to being killed in the preimplatation stagethan later. On the other side, the unborn is more susceptible to congenital
malformations when irradiated during the stage of maximum organogenesis
D . Cataractogenic Effects
The fibers which comprise the lens of the eye are specialized to transmit light. Damage
to these, and particularly to the developing immature cells which give rise to them, canresult in opacities in the lens called “cataracts,” which, if they are large enough, can
interfere with vision. Radiation in sufficiently high doses can induce the formation of
cataracts
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5. Radiation-Protection
Man benefits from the use of X rays, radioisotopes and fissionable materials in
industry, medicine, power generation and research. The realization of these gains
entails the exposure of persons to the radiation, and this involves a risk. The objective
of radiation protection is then to balance the risks and benefits from activities that
involve radiation
A proper system of management helps to maintain radioactive sources in good
physical status and provides means of source tracking and control.
The International Commission on Radiological Protection (ICRP) has developed some
specific radiation-protection standards. Different permissible exposure criteria are
usually applied to different groups of persons
Different probabilities exist for the occurrence of stochastic radiation effects in various
organs and tissues. This different sensitivity to stochastic radiation damage is
considered by the tissue weighting factor in calculations of the effective dose. To
calculate the effective dose, the individual organ dose values are multiplied by the
respective tissue weighting factor and the products added.
Table 3: ICRP Recommended Tissue Weighting Factors
Tissue WT
Bone marrow, colon, lung, Stomach,
Breast, Remainders (13 organs/tissues)
0.12
Gonads 0.08
Bladder, Oesophagus, Liver, Thyroid 0.04
Bone surface, Brain, Salivary glands, Skin 0.01
ICRP now considers that it is possible to define three categories of exposure situations,
namely: planned exposure situations which involve the deliberate introduction and
operation of sources; emergency exposure situations, which require urgent action in
order to avoid or reduce undesirable consequences; and existing exposure situations,
which include prolonged exposure situations after emergencies.
Radiation protection can be divided into occupational radiation protection, which is
the protection of workers, medical radiation protection, which is the protection of
patients and the radiographer, and public radiation protection, which is protection of
individual members of the public, and of the population as a whole
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Conclusion
All living matter is composed of atoms joined into molecules by electron bonds.
Ionizing radiation is energetic enough to displace atomic electrons and thus break the
bonds that hold a molecule together. This produces a number of chemical changes
that in the case of living cells, can lead to cell death or harmful effects
There are two different ways in which the radiation acts on the cell: direct and indirect
action. Direct effects are produced by the initial action of the radiation itself and
indirect effects are caused by the later chemical action of free radicals and other
radiation products
This action will lead to the biological effects. The biological effects of ionizing radiationcan be classified into deterministic effects (effects will increase with increasing doses)
and stochastic effects, in which the severity of the effect is independent of the
absorbed dose
Balancing the risks and benefits from activities that involve radiation is the main task of
the Radiation Protection. The International Commission on Radiological Protection
(ICRP) develops specific radiation-protection standards and recommended limits of
radiation exposure
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- International commission on radiation unitis and measurements – ICRU Report
16
- L. H. Van Vlack, Elements of Materials Science and Engineering, 5th ed.,
Addison-Wesley, 1985.
- International Comission of Radiological Protection (ICRP)