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Biological Effects
(Molecular and Cellular)
of Radiation
Nasu sowmya sree
Group – 10
Semesgter - 9
Guided by :
Skorobogatova mam
1
Radiations
• Radiation is energy that comes from a source and
travels through some material or through space.
• The different types of radiation differ only in their
respective wavelengths
• Low wavelength UV has the highest energy and is
potentially the most damaging
• Sunscreens can protect us from UV damage
3
The Electromagnetic Spectrum
We can see visible light.
We can feel the heat from IR and microwave radiation.
Our senses cannot detect most of the other wavelengths.
The Sun’s Radiation
• More than half of the sun’s radiation is in the IR
region of the spectrum
• Nearly 40% is in the visible region of the spectrum
• Only 8% is in the UV region, but this higher energy
radiation can potential cause damage to living cells
Types of radiations
5
6
Types of Radiation
• Radiation is classified into:
1. Ionizing radiation (nuclear radiation)
Alpha particles
Beta particles
Gamma rays (or photons)
X-Rays (or photons)
7
2.Non-ionizing Radiation Sources
Visible light
Microwaves
Radios
Video Display Terminals
Power lines
Radiofrequency Diathermy (Physical
Therapy)
Lasers 8
Ionizing Vs Non-ionizing
Radiation
Ionizing Radiation
– Higher energy electromagnetic waves
(gamma ) or heavy particles (beta and
alpha).
– High enough energy to pull electron
from orbit.
Non-ionizing Radiation
– Lower energy electromagnetic waves.
– Not enough energy to pull electron
from orbit, but can excite the electron.
9
Factors affecting biological activity
of radiations
• Penetrating power of radiations
• Tissue sensitivity
• Dose (energy) of radiations
• Surface area exposed
10
Moderately
radios ens itive
•Skin
•Vascular
endothelium
•Lung
•Kidney
•Liver
•Lens (eye)
Radiosensitivity of tissues
Highly
radios ens itive
•Lymphoid tissue
•Bone marrow
•Gastrointestinal
epithelium
•Gonads
•Embryonic tissues
Bone marrow S kin CN S
Least
radios ens itive
•Central nervous
system (CNS)
•Muscle
•Bone and
cartilage
•Connective tissue
Ionizing (nuclear) radiation
12
A radiation is said to be ionizing when it has enough
energy to eject one or more electrons from the atoms
or molecules in the irradiated medium.
This is the case of alpha and beta radiations, as well
as of electromagnetic radiations such as gamma
radiations, X-rays and some ultra-violet rays. Visible
or infrared light are not, nor are microwaves or radio
waves.
13
• Penetration in materials
– Outside the body, an alpha emitter is not a hazard
unless it is on the skin
– Inside the body, an alpha emitter is a bigger hazard if it
deposits its energy in sensitive tissue
14
Alpha rays
• C o m m o n alpha-particle emitters
– adon-222 ga s in the environment
– Uranium-234 and -238) in the
environment
– Polonium-210 in tobacco
• C o m m o n alpha-particle emitter uses
– Smoke detectors
– Cigarettes/cigars
S ou rc e s
Beta rays
• Penetration in materials
– At low energies, a beta particle is not very
penetrating – stopped by the outer layer of
skin or a piece of paper
– At higher energies, a beta particle may
penetrate to the live layer of skin .
– Inside the body, a beta particle is not as
hazardous as an alpha particle because it is
not as big
– Because it is not as big, it travels farther,
interacting with more tissue (but each small
piece of tissue gets less energy deposited17)
Gamma radiations
16
• Ionizing power is poor
• High penetrating power
• Form free radicals
• Injurious to health
X rays
Penetration power is sufficient to penetrate
tissues and can be detected outside.
Ionizing power is low
Properties of nuclear radiations
17
• High ionizing power- 1. alpha radiations
Moderate ionizing power- beta rad.
Low ionizing power- gamma & X rays
High penetrating power- gamma & X rays
Moderate penetrating power- Beta rays
Low penetrating power- alpha rays
18
• Radiation Causes Ionizations of:
ATOMS
which may affect
MOLECULES
which may affect
CELLS
which may affect
TISSUES
which may affect
ORGANS
which may affect
THE WHOLE BODY
19
20
Types of UV Radiation
Biological Effects of UV Radiation
The consequences depend primarily on:
1. The energy associated with the radiation
2. The length of time of the exposure
3. The sensitivity of the organism to that
radiation
The most deadly form of skin cancer,
melanoma, is linked with the intensity of
UV radiation and the latitude at which you
live.
Protection from UV Radiation
Effect of radiation on body
(1) Hair
The losing of hair quickly and in clumps occurs with
radiation exposure at 200 rems or higher.
(2) Brain
Since brain cells do not reproduce, they won't be
damaged directly unless the exposure is 5,000 rems
or greater. can cause seizures and immediate death.
(3) Thyroid
The thyroid gland is susceptible to radioactive
iodine. In sufficient amounts, radioactive iodine can
destroy all or part of the thyroid.
(4) Reproductive Tract
Because reproductive tract cells divide rapidly, these areas of
the body can be damaged at rem levels as low as 200. Long-
term, some radiation sickness victims will become sterile.28
(5) Blood System
When a person is exposed to around 100 rems, the blood's
lymphocyte cell count will be reduced, victim more susceptible to
infection. This refered to as mild radiation sickness. Early symptoms
of radiation sickness mimic those of flu.
According to data from Hiroshima and Nagaski, show that
symptoms may persist for up to 10 years and may also have an
increased long-term risk for leukemia and lymphoma.
(6) Heart
Intense exposure to radioactive material at 1,000 to 5,000 rems
would do immediate damage to small blood vessels and probably
cause heart failure and death directly.
(7) Gastrointestinal Tract
Radiation damage to the intestinal tract lining will cause nausea,
bloody vomiting and diarrhea. This is occurs when the victim's
exposure is 200 rems or more.
25
The Effects of Radiation on the
Cell at the Molecular Level
26
•When radiation interacts with target atoms,
energy is deposited, resulting in ionization
or excitation.
•The absorption of energy from ionizing
radiation produces damage to molecules by
direct and indirect actions.
•For direct action, da ma ge occurs a s a result
of ionization of atoms on key molecules in
the biologic system. This causes inactivation
or functional alteration of the molecule.
•Indirect action involves the production of
reactive free radiacals whose toxic dama ge
on the key molecule results in a biologic
effect.
Damage by ionising
radiation
• Indirect effect:
– Ionising event can break molecular
bonds but effect may manifest
elsewhere
– e.g. ionisation of water molecules can
produce free radicals (molecule with
unpaired electron in outer shell).
•Highly reactive
•Capable of diffusing a few micrometres to
reach and damage molecular bonds in
DNA
31
Indirect Action
28
• These are effects mediated by free
radicals.
• A free radical is an electrically
neutral atom with an unshared
electron in the orbital position. The
radical is electrophilic and highly
reactive. Since the predominant
molecule in biological systems is
water, it is usually the
intermediary of the radical
formation and propagation.
Indirect Action- Radiolysis of
Water
Free radicals readily recombine to electronic and orbital
neutrality. However, when many exist, as in high radiation
fluence, orbital neutrality can be achieved by:
1.Hydrogen radical dimerization (H2)
2.The formation of toxic hydrogen peroxide (H2O2).
3. The radical can also be transferred to an organic
molecule in the cell.
H-O-H ® H + + OH-
H-O-H ® H0 +OH0
29
(ionization)
(free radicals)
Indirect Action
30
• H0 + OH0 ®HOH (recombination)
• H0 + H0 ® H2 (dimer)
• OH0 + OH0 ® H2O2 (peroxide dimer)
• OH0 + RH ® R0 + HOH (Radical transfer)
• The presence of dissolved oxygen can modify
the reaction by enabling the creation of other
free radical species with greater stability and
lifetimes
• H0 +O2 ® HO2 (hydroperoxy free radical)
0
• R0 +O2 ®RO2 (organic peroxy free radical)
0
Indirect Action - The Lifetimes of Free
Radicals
• The lifetimes of simple free radicals (H0 or
OH0) are very short, on the order of 10-10
sec. While generally highly reactive they
do not exist long enough to migrate from
the site of formation to the cell nucleus.
However, the oxygen derived species
such as hydroperoxy free radical does not
readily recombine into neutral forms.
These more stable forms have a lifetime
long enough to migrate to the nucleus
where serious damage can occur.
31
Indirect Action- Free
Radicals
32
• The transfer of the free radical to a
biologic molecule can be sufficiently
damaging to cause bond breakage or
inactivation of key functions
• The organic
transfer the
peroxy
radical
free
form
radical can
molecule to
molecule causing damage at each
encounter. Thus a cumulative effect can
occur, greater than a single ionization
or broken bond.
BIOCHEMICAL REACTIONS WITH
IONIZING RADIATION
• DNA is the most important material
making up the chromosomes and
serves as the master blueprint for
the cell. It determines what types of
RNA are produced which, in turn,
determine the types of protein that
are produced.
I I
33
S-AT-S
I I
P P
I I
S-CG-S
I I
P P
I I
S-GC-S
I I
P P
I I
S-TA-S
I I
• There is considerable evidence
suggesting that DNA is the primary
target for cell damage from
ionizing radiation.
effects at low to moderate
(cell killing, mutagenesis,
• Toxic
doses
and malignant transformation)
appear to result from damage to
DNA. Thus, ionizing
cellular
radiation is
agent.
a classical genotoxic
38
• The lethal
35
and mutagenic effects of
moderate doses of radiation result
primarily from damage to cellular DNA.
• Although radiation can induce a variety
of DNA lesions including specific base
damage, it has long been assumed that
unrejoined DNA double strand breaks
are of primary importance in its
cytotoxic effects in mammalian cells.
• Active enzymatic repair processes exist
for the repair of both DNA base damage
and strand breaks. In many cases
breaks in the double-strand DNA can be
repaired by the enzymes, DNA
polymerase, and DNA ligase.
• The repair of double strand breaks is a
36
complex
recombinational
process involving
events, depending
upon the nature of the initial break.
• Residual unrejoined double strand
breaks are lethal to the cell, whereas
incorrectly recoined breaks may
produce important mutagenic lesions. In
many cases, this DNA misrepair
apparently leads to DNA deletions and
rearrangements. Such large-scale
changes in DNA structure are
characteristic of most radiation induced
mutations.
37
Radiation Induced Chromosome
D a m a g e
38
•Chromosomes are composed of
deoxyribonucleic acid (DNA), a
macromolecule containing genetic
information. This large, tightly coiled,
double stranded molecule is sensitive to
radiation damage. Radiation effects
range from complete breaks of the
nucleotide chains of DNA, to point
mutations which are essentially radiation-
induced chemical changes in the
nucleotides which may not affect the
integrity of the basic structure.
Radiation Induced Chromosome
D a m a g e
39
• After irradiation, chromosomes may appear to
be "sticky" with formation of temporary or
permanent
preventing normal
interchromosomal bridges
chromosome separation
during mitosis and transcription
addition, radiation
of genetic
can cause
information. In
structural aberrations with pieces of the
chromosomes break and form aberrant shapes.
Unequal division of nuclear chromatin material
between daughter cells may result in production
of nonviable, abnormal nuclei.
Radiation Induced Membrane
40
D am ag e
• Biological membranes serve as highly specific
mediators between the cell (or its organelles)
and the environment. Alterations in the
proteins that form part of a membrane ’
s
changes in its
structure can cause
permeability molecules, i.e.,
electrolytes. In
to various
the case of nerve cells, this
would affect their ability to conduct electrical
impulses. In the case of lysosomes, the
unregulated release of its catabolic enzymes
into the cell could be disastrous. Ionizing
radiation has been suggested as playing a role
in plasma membrane damage, which may be
an important factor in cell death (interphase
death)
Cell Cycle
41
• Irradiation of the cell causes cell
death at mitosis as a result of the
inability to divide.(Mitotic death)
• RNA and protein synthesis do not
halt in the sterilized cell. The result
is the production of the giant cell,
whose unbalanced growth
eventually proves lethal to the cell.
applications
42
• Contrast media and diagnosis
• Therapeutic applications
teletherapy: removal of lesions not possible by
surgery (gamma)
surface source: dermatologic and ophthalmic use
(beta)
extracorporeal (on blood vessels): change in
immune response (x ray)
infusions: to treat peritoneal and pleural diffusion
in malignant tumours (gamma and beta ray)
Thank you

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radiationlecture-170227063014.pptx

  • 1. Biological Effects (Molecular and Cellular) of Radiation Nasu sowmya sree Group – 10 Semesgter - 9 Guided by : Skorobogatova mam 1
  • 2. Radiations • Radiation is energy that comes from a source and travels through some material or through space. • The different types of radiation differ only in their respective wavelengths • Low wavelength UV has the highest energy and is potentially the most damaging • Sunscreens can protect us from UV damage 3
  • 3. The Electromagnetic Spectrum We can see visible light. We can feel the heat from IR and microwave radiation. Our senses cannot detect most of the other wavelengths.
  • 4. The Sun’s Radiation • More than half of the sun’s radiation is in the IR region of the spectrum • Nearly 40% is in the visible region of the spectrum • Only 8% is in the UV region, but this higher energy radiation can potential cause damage to living cells
  • 6. 6
  • 7. Types of Radiation • Radiation is classified into: 1. Ionizing radiation (nuclear radiation) Alpha particles Beta particles Gamma rays (or photons) X-Rays (or photons) 7
  • 8. 2.Non-ionizing Radiation Sources Visible light Microwaves Radios Video Display Terminals Power lines Radiofrequency Diathermy (Physical Therapy) Lasers 8
  • 9. Ionizing Vs Non-ionizing Radiation Ionizing Radiation – Higher energy electromagnetic waves (gamma ) or heavy particles (beta and alpha). – High enough energy to pull electron from orbit. Non-ionizing Radiation – Lower energy electromagnetic waves. – Not enough energy to pull electron from orbit, but can excite the electron. 9
  • 10. Factors affecting biological activity of radiations • Penetrating power of radiations • Tissue sensitivity • Dose (energy) of radiations • Surface area exposed 10
  • 11. Moderately radios ens itive •Skin •Vascular endothelium •Lung •Kidney •Liver •Lens (eye) Radiosensitivity of tissues Highly radios ens itive •Lymphoid tissue •Bone marrow •Gastrointestinal epithelium •Gonads •Embryonic tissues Bone marrow S kin CN S Least radios ens itive •Central nervous system (CNS) •Muscle •Bone and cartilage •Connective tissue
  • 12. Ionizing (nuclear) radiation 12 A radiation is said to be ionizing when it has enough energy to eject one or more electrons from the atoms or molecules in the irradiated medium. This is the case of alpha and beta radiations, as well as of electromagnetic radiations such as gamma radiations, X-rays and some ultra-violet rays. Visible or infrared light are not, nor are microwaves or radio waves.
  • 13. 13
  • 14. • Penetration in materials – Outside the body, an alpha emitter is not a hazard unless it is on the skin – Inside the body, an alpha emitter is a bigger hazard if it deposits its energy in sensitive tissue 14 Alpha rays • C o m m o n alpha-particle emitters – adon-222 ga s in the environment – Uranium-234 and -238) in the environment – Polonium-210 in tobacco • C o m m o n alpha-particle emitter uses – Smoke detectors – Cigarettes/cigars S ou rc e s
  • 15. Beta rays • Penetration in materials – At low energies, a beta particle is not very penetrating – stopped by the outer layer of skin or a piece of paper – At higher energies, a beta particle may penetrate to the live layer of skin . – Inside the body, a beta particle is not as hazardous as an alpha particle because it is not as big – Because it is not as big, it travels farther, interacting with more tissue (but each small piece of tissue gets less energy deposited17)
  • 16. Gamma radiations 16 • Ionizing power is poor • High penetrating power • Form free radicals • Injurious to health X rays Penetration power is sufficient to penetrate tissues and can be detected outside. Ionizing power is low
  • 17. Properties of nuclear radiations 17 • High ionizing power- 1. alpha radiations Moderate ionizing power- beta rad. Low ionizing power- gamma & X rays High penetrating power- gamma & X rays Moderate penetrating power- Beta rays Low penetrating power- alpha rays
  • 18. 18
  • 19. • Radiation Causes Ionizations of: ATOMS which may affect MOLECULES which may affect CELLS which may affect TISSUES which may affect ORGANS which may affect THE WHOLE BODY 19
  • 20. 20
  • 21. Types of UV Radiation
  • 22. Biological Effects of UV Radiation The consequences depend primarily on: 1. The energy associated with the radiation 2. The length of time of the exposure 3. The sensitivity of the organism to that radiation The most deadly form of skin cancer, melanoma, is linked with the intensity of UV radiation and the latitude at which you live.
  • 23. Protection from UV Radiation
  • 24. Effect of radiation on body (1) Hair The losing of hair quickly and in clumps occurs with radiation exposure at 200 rems or higher. (2) Brain Since brain cells do not reproduce, they won't be damaged directly unless the exposure is 5,000 rems or greater. can cause seizures and immediate death. (3) Thyroid The thyroid gland is susceptible to radioactive iodine. In sufficient amounts, radioactive iodine can destroy all or part of the thyroid. (4) Reproductive Tract Because reproductive tract cells divide rapidly, these areas of the body can be damaged at rem levels as low as 200. Long- term, some radiation sickness victims will become sterile.28
  • 25. (5) Blood System When a person is exposed to around 100 rems, the blood's lymphocyte cell count will be reduced, victim more susceptible to infection. This refered to as mild radiation sickness. Early symptoms of radiation sickness mimic those of flu. According to data from Hiroshima and Nagaski, show that symptoms may persist for up to 10 years and may also have an increased long-term risk for leukemia and lymphoma. (6) Heart Intense exposure to radioactive material at 1,000 to 5,000 rems would do immediate damage to small blood vessels and probably cause heart failure and death directly. (7) Gastrointestinal Tract Radiation damage to the intestinal tract lining will cause nausea, bloody vomiting and diarrhea. This is occurs when the victim's exposure is 200 rems or more. 25
  • 26. The Effects of Radiation on the Cell at the Molecular Level 26 •When radiation interacts with target atoms, energy is deposited, resulting in ionization or excitation. •The absorption of energy from ionizing radiation produces damage to molecules by direct and indirect actions. •For direct action, da ma ge occurs a s a result of ionization of atoms on key molecules in the biologic system. This causes inactivation or functional alteration of the molecule. •Indirect action involves the production of reactive free radiacals whose toxic dama ge on the key molecule results in a biologic effect.
  • 27. Damage by ionising radiation • Indirect effect: – Ionising event can break molecular bonds but effect may manifest elsewhere – e.g. ionisation of water molecules can produce free radicals (molecule with unpaired electron in outer shell). •Highly reactive •Capable of diffusing a few micrometres to reach and damage molecular bonds in DNA 31
  • 28. Indirect Action 28 • These are effects mediated by free radicals. • A free radical is an electrically neutral atom with an unshared electron in the orbital position. The radical is electrophilic and highly reactive. Since the predominant molecule in biological systems is water, it is usually the intermediary of the radical formation and propagation.
  • 29. Indirect Action- Radiolysis of Water Free radicals readily recombine to electronic and orbital neutrality. However, when many exist, as in high radiation fluence, orbital neutrality can be achieved by: 1.Hydrogen radical dimerization (H2) 2.The formation of toxic hydrogen peroxide (H2O2). 3. The radical can also be transferred to an organic molecule in the cell. H-O-H ® H + + OH- H-O-H ® H0 +OH0 29 (ionization) (free radicals)
  • 30. Indirect Action 30 • H0 + OH0 ®HOH (recombination) • H0 + H0 ® H2 (dimer) • OH0 + OH0 ® H2O2 (peroxide dimer) • OH0 + RH ® R0 + HOH (Radical transfer) • The presence of dissolved oxygen can modify the reaction by enabling the creation of other free radical species with greater stability and lifetimes • H0 +O2 ® HO2 (hydroperoxy free radical) 0 • R0 +O2 ®RO2 (organic peroxy free radical) 0
  • 31. Indirect Action - The Lifetimes of Free Radicals • The lifetimes of simple free radicals (H0 or OH0) are very short, on the order of 10-10 sec. While generally highly reactive they do not exist long enough to migrate from the site of formation to the cell nucleus. However, the oxygen derived species such as hydroperoxy free radical does not readily recombine into neutral forms. These more stable forms have a lifetime long enough to migrate to the nucleus where serious damage can occur. 31
  • 32. Indirect Action- Free Radicals 32 • The transfer of the free radical to a biologic molecule can be sufficiently damaging to cause bond breakage or inactivation of key functions • The organic transfer the peroxy radical free form radical can molecule to molecule causing damage at each encounter. Thus a cumulative effect can occur, greater than a single ionization or broken bond.
  • 33. BIOCHEMICAL REACTIONS WITH IONIZING RADIATION • DNA is the most important material making up the chromosomes and serves as the master blueprint for the cell. It determines what types of RNA are produced which, in turn, determine the types of protein that are produced. I I 33 S-AT-S I I P P I I S-CG-S I I P P I I S-GC-S I I P P I I S-TA-S I I
  • 34. • There is considerable evidence suggesting that DNA is the primary target for cell damage from ionizing radiation. effects at low to moderate (cell killing, mutagenesis, • Toxic doses and malignant transformation) appear to result from damage to DNA. Thus, ionizing cellular radiation is agent. a classical genotoxic 38
  • 35. • The lethal 35 and mutagenic effects of moderate doses of radiation result primarily from damage to cellular DNA. • Although radiation can induce a variety of DNA lesions including specific base damage, it has long been assumed that unrejoined DNA double strand breaks are of primary importance in its cytotoxic effects in mammalian cells.
  • 36. • Active enzymatic repair processes exist for the repair of both DNA base damage and strand breaks. In many cases breaks in the double-strand DNA can be repaired by the enzymes, DNA polymerase, and DNA ligase. • The repair of double strand breaks is a 36 complex recombinational process involving events, depending upon the nature of the initial break.
  • 37. • Residual unrejoined double strand breaks are lethal to the cell, whereas incorrectly recoined breaks may produce important mutagenic lesions. In many cases, this DNA misrepair apparently leads to DNA deletions and rearrangements. Such large-scale changes in DNA structure are characteristic of most radiation induced mutations. 37
  • 38. Radiation Induced Chromosome D a m a g e 38 •Chromosomes are composed of deoxyribonucleic acid (DNA), a macromolecule containing genetic information. This large, tightly coiled, double stranded molecule is sensitive to radiation damage. Radiation effects range from complete breaks of the nucleotide chains of DNA, to point mutations which are essentially radiation- induced chemical changes in the nucleotides which may not affect the integrity of the basic structure.
  • 39. Radiation Induced Chromosome D a m a g e 39 • After irradiation, chromosomes may appear to be "sticky" with formation of temporary or permanent preventing normal interchromosomal bridges chromosome separation during mitosis and transcription addition, radiation of genetic can cause information. In structural aberrations with pieces of the chromosomes break and form aberrant shapes. Unequal division of nuclear chromatin material between daughter cells may result in production of nonviable, abnormal nuclei.
  • 40. Radiation Induced Membrane 40 D am ag e • Biological membranes serve as highly specific mediators between the cell (or its organelles) and the environment. Alterations in the proteins that form part of a membrane ’ s changes in its structure can cause permeability molecules, i.e., electrolytes. In to various the case of nerve cells, this would affect their ability to conduct electrical impulses. In the case of lysosomes, the unregulated release of its catabolic enzymes into the cell could be disastrous. Ionizing radiation has been suggested as playing a role in plasma membrane damage, which may be an important factor in cell death (interphase death)
  • 41. Cell Cycle 41 • Irradiation of the cell causes cell death at mitosis as a result of the inability to divide.(Mitotic death) • RNA and protein synthesis do not halt in the sterilized cell. The result is the production of the giant cell, whose unbalanced growth eventually proves lethal to the cell.
  • 42. applications 42 • Contrast media and diagnosis • Therapeutic applications teletherapy: removal of lesions not possible by surgery (gamma) surface source: dermatologic and ophthalmic use (beta) extracorporeal (on blood vessels): change in immune response (x ray) infusions: to treat peritoneal and pleural diffusion in malignant tumours (gamma and beta ray)