Biological Effects of Ionizing Radiation_Laura J.

7/27/2019 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



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.



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".

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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



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

Bibliography

- UW Environmental Health and Safety- (2006, January) Principles of Radiation

Protection

- Hall, E.J. (1988) Radiobiology for the Radiologist , J.B. Lippincott Co.,

Philadelphia.

- Física nuclear y de Partículas- A.Ferrer 2ºEdicion

- International commission on radiation unitis and measurements – ICRU Report

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- L. H. Van Vlack, Elements of Materials Science and Engineering, 5th ed.,

Addison-Wesley, 1985.

- International Comission of Radiological Protection (ICRP)

Biological Effects of Ionizing Radiation_Laura J.

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