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RADIATION, NUCLEAR
AND NANO MEDICINES
BY
T.R.DIVYA m.sc
Bharathidasan university
MY TOPIC
ISOTOPES
RADIOISOTOPES
RADIOACTVE DECAY
HALF LIFE
DIRECT AND INDIRECT ACTION OF RADIATION
RADIATION INDUCED DAMAGE
REPAIR OF RADIATION INDUCED DAMAGE
INTRODUCTION
• INTRODUCTION ABOUT RADIATION:
Radiation is energy in the form of waves or
streams of particles.
Based on the interaction with the matter
there are two types of radiation
1. Ionizing radiation
2. Non- ionizing radiation
TYPES OF RADIATION
ATOMS
• Where all matter begins?
Atoms are the basic building blocks of the
all the matters in this world.
All things both living and non living begins
with atoms only.
Atoms are elements like oxygen ,
hydrogen and carbon.
STRUCTURE OF AN ATOM
ISOTOPES
• An isotopes is a variant of a particular
chemical element.
• Isotopes of an element consists of a same
number of protons and different number of
neutrons.
• For example, hydrogen has 3 isotopes:
Hydrogen 1 : 1 proton and no neutrons
Hydrogen 2 : 1 proton and 1 neutron
Hydrogen 3 : 1 proton and 2 neutrons
Isotope is stable when
it has a stable number
of neutrons and
protons.
The number of
protons present in
atom is also called
as Atomic
number.
RADIOISOTOPE
DEFINITION:
• Radioactive isotope or radioisotope, natural or
artificially created isotope of a chemical element
having an unstable nucleus that decays emitting
α,β and ϒ rays until stability reached
• A radioisotope is an isotope of an element that
undergoes spontaneous decay and emits
radiation as it decays.
• During the decay process , it becomes less
radioactive overtime, eventually becoming stable.
• Once an atom reaches a stable configuration, it
no longer gives off radiation.
RADIOACTIVE DECAY
• Radioactive decay is the process in which an
unstable atomic nucleus loses energy by
emitting radiation in the form of particles or
electromagnetic waves.
• There are two forms of radioactive decay
Natural radioactivity
Artificial radioactivity
RADIOACTIVE DECAY
• Natural radioactivity:
This is the spontaneous disintegration of
naturally occurring radio–nuclides to form a
more stable nuclide with the emission of
radiations of alpha, beta and gamma.
• Artificial radioactivity:
This is the spontaneous disintegration of a
nuclide when bombarded with a fast moving
thermal neutron to produce a new nuclide
with the emission of radiations of alpha, beta
and gamma and a large amount heat.
RADIOACTIVE DECAY
• There are three types of radioactive decays:
α decay
β decay
ϒ decay
RADIOACTIVE DECAY
RADIOACTIVE DECAY
α – decay:
• Alpha particles consists of large mass. Alpha
decay occurs when the atom ejects a particle
from the nucleus ,which consists of two
neutrons and two protons.
• When alpha decay occurs , the atomic number
decreases up to 2 and the mass decreases by
4.
• Electrical charge of +2
RADIOACTIVE DECAY
• E.g., Radon-222
• Another example:
RADIOACTIVE DECAY
β – decay:
β particles are consists of small mass and -1
electrical charge. It is mainly emitted by
nucleus.
In basic β – decay, a neutron is turned into a
proton and an electron is emitted from the
nucleus.
The atomic number increases by 1 and mass
decreases slightly.
E.g., Iodine – 131 which is used in
detection and treatment of thyroid cancer.
RADIOACTIVE DECAY
ϒ – emission:
Gamma radiation have high energy , short
wave length. It accompanies with alpha and
beta emission ,but it’s usually not shown in a
balanced nuclear reaction.
Gamma is an electromagnetic wave or
photon which has no electrical charge and has
great penetrating power.
Gamma decay takes place when there is
residual energy in the nucleus following α or β
decay.
RADIOACTIVE DECAY
• The residual energy is released as a photon of
gamma radiation. Gamma decay generally
does not affect the mass or atomic number of
a radioisotope.
• Gamma radiation is similar to that of X- rays.
• E.g., Cobalt- 60(Co-60). Gamma rays are
focused on the tumor to destroy it.
HALF LIFE
• Radioactive half-life is the time it takes half
the radioactive atoms present to decay.
Before After one half-life
DIRECT AND INDIRECT ACTION OF
RADIATION
• When any form of radiation whether it is
charged or uncharged particles is absorbed in
biological material , there is a possibility that it
will interact directly with the critical targets in
the cells.
• There are chances for two types of actions:
Direct action
Indirect action
DIRECT AND INDIRECT ACTION OF
RADIATION
DIRECT ACTION:
• The atoms of the target itself may be
ionized or excited , thus initiating the chain of
events that leads to a biological change.
• In direct action a secondary electron
resulting from absorption of an X- ray photon
interacts with the DNA to produce an effect.
DIRECT AND INDIRECT ACTION OF
RADIATION
INDIRECT ACTION:
• If the radiation interacts with other
atoms or molecules in the cell(particularly
water) to produce free radicals that are able
to diffuse far enough to damage the targets.
• In indirect action the secondary
electrons interacts with for e.g., a water
molecule and produce a hydroxyl radicals ,
which turn produces the damage to the DNA.
DIRECT AND INDIRECT ACTION OF
RADIATION
RADIATION INDUCED DAMAGE
INTRODUCTION:
• Radiation damage to cells in the body can
happen after a person receives radiation therapy
to treat cancer.
• It can also happen if a person exposed to
radiation through X-ray imaging , nuclear power
or fallout from nuclear weapons.
• If severe enough radiation damage may
cause cancer , birth defects and other serious
problems.
• DNA is the major target of radiation
induced damage.
RADIATION INDUCED DAMAGE
• There are three types of radiation induced
damage:
Lethal
Potentially lethal
Sub- lethal
RADIATION INDUCED DAMAGE
Lethal damage:
• This is irreversible and irreparable and leads
to cell death.
Potentially lethal damage:
• The cells can repaired if allowed to remain in
the stationary phase for some time after
irradiation.
• Component of radiation damage that can be
modified by post-irradiation environmental
conditions.
• Damage considered being potentially lethal
since under ordinary circumstances leads to cell
death.
RADIATION INDUCED DAMAGE
• If cells were maintained in sub-optimal
conditions; do not have to attempt mitosis while
chromosomes are expressing radiation-induced
injury.
• This delay leads to repair of the DNA damage
and increased survival.
• Sub – lethal:
• The cell can repair itself.
• Under normal circumstances this can be
repaired in hours, usually considered to be
complete within 24 hours.
RADIATION INDUCED DAMAGE
• If additional sub-lethal damage added within
this time then can interact to form lethal damage.
Stochastic effect:
• Stochastic effects are those that occur by
chance and consist primarily of cancer and
genetic effects.
• Stochastic effects are coincidental and
cannot be avoided
• These can be divided into somatic and
genetic.
EFFECTS OF RADIATION
EFFECTS OF RADIATION
Deterministic effect:
• Deterministic effects have a threshold of
irradiation under which they do not appear
and are the necessary consequence of
irradiation.
• The damage they cause depends on the
doses.
EFFECTS OF RADIATION
RADIATION DOSE ( IN
GRAYS)
EFFECTS DURATION FOR
DEATH
1 Gy and 2 Gy NVD syndrome Nausea, vomiting and
diarrhoea.
2-6 Gy Hematopoietic
syndrome
10 to 30 days
8-15 Gy Gastrointestinal (GI)
syndrome
3-5 days
above 25 Gy Central nervous system
(CNS) syndrome
within 48 hrs
OTHER EFFECTS OF RADIATION
• If death doesn’t occur there are other effects
of radiation:
• i. Generation of free radicals
• ii. Breakage of chemical bonds
• iii. Formation of new chemical bonds and
cross-linkage between macromolecules.
• iv. Damage to bio molecules (e.g. DNA, RNA,
lipids, proteins) which regulate vital cell
processes
S.No. Type of Damage Examples
1 Single-base alteration A.Depurination
B.Deamination of cytosine to uracil
C.Deamination of adenine to hypoxanthine
D.Alkylation of base
E.Insertion or deletion of nucleotide
F.Base-analog incorporation
2 Two-base alterations A. UV light–induced thymine-thymine
(pyrimidine) dimer
B. Bifunctional Alkylating agent cross-linkage
3 Chain breaks A. Ionizing radiation
B. Radioactive disintegration of backbone
element
C. Oxidative free radical formation
4 Cross-linkage A. Between bases in same or opposite strands
B. Between DNA and protein molecules (eg,
histones)
REPAIR OF RADIATION INDUCED DNA
DAMAGE
DNA repair can be grouped into two major
functional categories:
Direct Damage reversal
Excision of DNA damage
REPAIR OF RADIATION INDUCED DNA
DAMAGE
DIRECT DAMAGE REVERSAL
• The direct reversal of DNA damage is by far the
simplest repair mechanism that involves a single
polypeptide chain, with enzymatic properties
which binds to the damage and restores the DNA
genome to its normal state in a single-reaction
step.
• The major polypeptides involved in this pathway
are
• i) DNA photolyases
• ii) O6-methylguanine-DNA
methyltransferase I and II (MGMT), also called
DNA-alkyltransferases
DNA PHOTOLYASES
EXCISION OF DNA DAMAGE
There are four types of excision repair:
i) Base excision repair (BER)
ii) Nucleotide excision repair (NER),
iii) Mismatch repair (MMR) and
iv) Strand break repairs.
• In these reactions a nucleotide segment
containing base damage, double-helix distortion
or impaired bases are replaced by the normal
nucleotide sequence in a new DNA polymerase
synthesis process.
BASE EXCISION REPAIR
Base excision-repair of DNA
•The enzyme uracil DNA
glycosylase removes the uracil
created by spontaneous
deamination of cytosine in the
DNA.
•An endonuclease cuts the
backbone near the defect
•An endonuclease removes a
few bases
•The defect is filled in by the
action of a DNA polymerase and
•The strand is rejoined by a
ligase.
NUCLEOTIDE EXCISION REPAIR
• In eukaryotic cells the
enzymes cut between the
third to fifth phosphodiester
bond 3' from the lesion, and
on the 5' side the cut is
somewhere between the
twenty-first and twenty-fifth
bonds.
• Thus, a fragment of DNA 27–
29 nucleotides long is excised.
• After the strand is removed it
is replaced, again by exact
base pairing, through the
action of yet another
polymerase, and the ends are
joined to the existing strands
by DNA ligase.
MISMATCH REPAIR
• This mechanism corrects a
single mismatch base pair
(e.g., C to A rather than T
to A) or a short region of
unpaired DNA.
• The defective region is
recognized by an
endonuclease that makes a
single-strand cut at an
adjacent methylated GATC
sequence.
• The DNA strand is removed
through the mutation,
replaced, and religated.
BREAKING STRANDS REPAIR
• Ionizing radiation can produce both single-
strand breaks (SSBs) and double-strand breaks
(DSBs) in the DNA backbone.
SINGLE STRAND BREAK REPAIR:
• Breaks in a single strand of the DNA molecule
are repaired using the same enzyme systems
that are used in Base-Excision Repair (BER).
TYPES OF DSBs REPAIRS
THANK YOU…..

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Radiation basics and radiation damage

  • 1. RADIATION, NUCLEAR AND NANO MEDICINES BY T.R.DIVYA m.sc Bharathidasan university
  • 2. MY TOPIC ISOTOPES RADIOISOTOPES RADIOACTVE DECAY HALF LIFE DIRECT AND INDIRECT ACTION OF RADIATION RADIATION INDUCED DAMAGE REPAIR OF RADIATION INDUCED DAMAGE
  • 3. INTRODUCTION • INTRODUCTION ABOUT RADIATION: Radiation is energy in the form of waves or streams of particles. Based on the interaction with the matter there are two types of radiation 1. Ionizing radiation 2. Non- ionizing radiation
  • 5. ATOMS • Where all matter begins? Atoms are the basic building blocks of the all the matters in this world. All things both living and non living begins with atoms only. Atoms are elements like oxygen , hydrogen and carbon.
  • 7. ISOTOPES • An isotopes is a variant of a particular chemical element. • Isotopes of an element consists of a same number of protons and different number of neutrons. • For example, hydrogen has 3 isotopes: Hydrogen 1 : 1 proton and no neutrons Hydrogen 2 : 1 proton and 1 neutron Hydrogen 3 : 1 proton and 2 neutrons
  • 8. Isotope is stable when it has a stable number of neutrons and protons. The number of protons present in atom is also called as Atomic number.
  • 9. RADIOISOTOPE DEFINITION: • Radioactive isotope or radioisotope, natural or artificially created isotope of a chemical element having an unstable nucleus that decays emitting α,β and ϒ rays until stability reached • A radioisotope is an isotope of an element that undergoes spontaneous decay and emits radiation as it decays. • During the decay process , it becomes less radioactive overtime, eventually becoming stable. • Once an atom reaches a stable configuration, it no longer gives off radiation.
  • 10. RADIOACTIVE DECAY • Radioactive decay is the process in which an unstable atomic nucleus loses energy by emitting radiation in the form of particles or electromagnetic waves. • There are two forms of radioactive decay Natural radioactivity Artificial radioactivity
  • 11. RADIOACTIVE DECAY • Natural radioactivity: This is the spontaneous disintegration of naturally occurring radio–nuclides to form a more stable nuclide with the emission of radiations of alpha, beta and gamma. • Artificial radioactivity: This is the spontaneous disintegration of a nuclide when bombarded with a fast moving thermal neutron to produce a new nuclide with the emission of radiations of alpha, beta and gamma and a large amount heat.
  • 12. RADIOACTIVE DECAY • There are three types of radioactive decays: α decay β decay ϒ decay
  • 14. RADIOACTIVE DECAY α – decay: • Alpha particles consists of large mass. Alpha decay occurs when the atom ejects a particle from the nucleus ,which consists of two neutrons and two protons. • When alpha decay occurs , the atomic number decreases up to 2 and the mass decreases by 4. • Electrical charge of +2
  • 15. RADIOACTIVE DECAY • E.g., Radon-222 • Another example:
  • 16. RADIOACTIVE DECAY β – decay: β particles are consists of small mass and -1 electrical charge. It is mainly emitted by nucleus. In basic β – decay, a neutron is turned into a proton and an electron is emitted from the nucleus. The atomic number increases by 1 and mass decreases slightly. E.g., Iodine – 131 which is used in detection and treatment of thyroid cancer.
  • 17. RADIOACTIVE DECAY ϒ – emission: Gamma radiation have high energy , short wave length. It accompanies with alpha and beta emission ,but it’s usually not shown in a balanced nuclear reaction. Gamma is an electromagnetic wave or photon which has no electrical charge and has great penetrating power. Gamma decay takes place when there is residual energy in the nucleus following α or β decay.
  • 18. RADIOACTIVE DECAY • The residual energy is released as a photon of gamma radiation. Gamma decay generally does not affect the mass or atomic number of a radioisotope. • Gamma radiation is similar to that of X- rays. • E.g., Cobalt- 60(Co-60). Gamma rays are focused on the tumor to destroy it.
  • 19. HALF LIFE • Radioactive half-life is the time it takes half the radioactive atoms present to decay. Before After one half-life
  • 20. DIRECT AND INDIRECT ACTION OF RADIATION • When any form of radiation whether it is charged or uncharged particles is absorbed in biological material , there is a possibility that it will interact directly with the critical targets in the cells. • There are chances for two types of actions: Direct action Indirect action
  • 21. DIRECT AND INDIRECT ACTION OF RADIATION DIRECT ACTION: • The atoms of the target itself may be ionized or excited , thus initiating the chain of events that leads to a biological change. • In direct action a secondary electron resulting from absorption of an X- ray photon interacts with the DNA to produce an effect.
  • 22. DIRECT AND INDIRECT ACTION OF RADIATION INDIRECT ACTION: • If the radiation interacts with other atoms or molecules in the cell(particularly water) to produce free radicals that are able to diffuse far enough to damage the targets. • In indirect action the secondary electrons interacts with for e.g., a water molecule and produce a hydroxyl radicals , which turn produces the damage to the DNA.
  • 23. DIRECT AND INDIRECT ACTION OF RADIATION
  • 24.
  • 25.
  • 26. RADIATION INDUCED DAMAGE INTRODUCTION: • Radiation damage to cells in the body can happen after a person receives radiation therapy to treat cancer. • It can also happen if a person exposed to radiation through X-ray imaging , nuclear power or fallout from nuclear weapons. • If severe enough radiation damage may cause cancer , birth defects and other serious problems. • DNA is the major target of radiation induced damage.
  • 27. RADIATION INDUCED DAMAGE • There are three types of radiation induced damage: Lethal Potentially lethal Sub- lethal
  • 28. RADIATION INDUCED DAMAGE Lethal damage: • This is irreversible and irreparable and leads to cell death. Potentially lethal damage: • The cells can repaired if allowed to remain in the stationary phase for some time after irradiation. • Component of radiation damage that can be modified by post-irradiation environmental conditions. • Damage considered being potentially lethal since under ordinary circumstances leads to cell death.
  • 29. RADIATION INDUCED DAMAGE • If cells were maintained in sub-optimal conditions; do not have to attempt mitosis while chromosomes are expressing radiation-induced injury. • This delay leads to repair of the DNA damage and increased survival. • Sub – lethal: • The cell can repair itself. • Under normal circumstances this can be repaired in hours, usually considered to be complete within 24 hours.
  • 30. RADIATION INDUCED DAMAGE • If additional sub-lethal damage added within this time then can interact to form lethal damage. Stochastic effect: • Stochastic effects are those that occur by chance and consist primarily of cancer and genetic effects. • Stochastic effects are coincidental and cannot be avoided • These can be divided into somatic and genetic. EFFECTS OF RADIATION
  • 31. EFFECTS OF RADIATION Deterministic effect: • Deterministic effects have a threshold of irradiation under which they do not appear and are the necessary consequence of irradiation. • The damage they cause depends on the doses.
  • 32. EFFECTS OF RADIATION RADIATION DOSE ( IN GRAYS) EFFECTS DURATION FOR DEATH 1 Gy and 2 Gy NVD syndrome Nausea, vomiting and diarrhoea. 2-6 Gy Hematopoietic syndrome 10 to 30 days 8-15 Gy Gastrointestinal (GI) syndrome 3-5 days above 25 Gy Central nervous system (CNS) syndrome within 48 hrs
  • 33. OTHER EFFECTS OF RADIATION • If death doesn’t occur there are other effects of radiation: • i. Generation of free radicals • ii. Breakage of chemical bonds • iii. Formation of new chemical bonds and cross-linkage between macromolecules. • iv. Damage to bio molecules (e.g. DNA, RNA, lipids, proteins) which regulate vital cell processes
  • 34.
  • 35. S.No. Type of Damage Examples 1 Single-base alteration A.Depurination B.Deamination of cytosine to uracil C.Deamination of adenine to hypoxanthine D.Alkylation of base E.Insertion or deletion of nucleotide F.Base-analog incorporation 2 Two-base alterations A. UV light–induced thymine-thymine (pyrimidine) dimer B. Bifunctional Alkylating agent cross-linkage 3 Chain breaks A. Ionizing radiation B. Radioactive disintegration of backbone element C. Oxidative free radical formation 4 Cross-linkage A. Between bases in same or opposite strands B. Between DNA and protein molecules (eg, histones)
  • 36. REPAIR OF RADIATION INDUCED DNA DAMAGE DNA repair can be grouped into two major functional categories: Direct Damage reversal Excision of DNA damage
  • 37. REPAIR OF RADIATION INDUCED DNA DAMAGE
  • 38. DIRECT DAMAGE REVERSAL • The direct reversal of DNA damage is by far the simplest repair mechanism that involves a single polypeptide chain, with enzymatic properties which binds to the damage and restores the DNA genome to its normal state in a single-reaction step. • The major polypeptides involved in this pathway are • i) DNA photolyases • ii) O6-methylguanine-DNA methyltransferase I and II (MGMT), also called DNA-alkyltransferases
  • 40. EXCISION OF DNA DAMAGE There are four types of excision repair: i) Base excision repair (BER) ii) Nucleotide excision repair (NER), iii) Mismatch repair (MMR) and iv) Strand break repairs. • In these reactions a nucleotide segment containing base damage, double-helix distortion or impaired bases are replaced by the normal nucleotide sequence in a new DNA polymerase synthesis process.
  • 41. BASE EXCISION REPAIR Base excision-repair of DNA •The enzyme uracil DNA glycosylase removes the uracil created by spontaneous deamination of cytosine in the DNA. •An endonuclease cuts the backbone near the defect •An endonuclease removes a few bases •The defect is filled in by the action of a DNA polymerase and •The strand is rejoined by a ligase.
  • 42. NUCLEOTIDE EXCISION REPAIR • In eukaryotic cells the enzymes cut between the third to fifth phosphodiester bond 3' from the lesion, and on the 5' side the cut is somewhere between the twenty-first and twenty-fifth bonds. • Thus, a fragment of DNA 27– 29 nucleotides long is excised. • After the strand is removed it is replaced, again by exact base pairing, through the action of yet another polymerase, and the ends are joined to the existing strands by DNA ligase.
  • 43. MISMATCH REPAIR • This mechanism corrects a single mismatch base pair (e.g., C to A rather than T to A) or a short region of unpaired DNA. • The defective region is recognized by an endonuclease that makes a single-strand cut at an adjacent methylated GATC sequence. • The DNA strand is removed through the mutation, replaced, and religated.
  • 44. BREAKING STRANDS REPAIR • Ionizing radiation can produce both single- strand breaks (SSBs) and double-strand breaks (DSBs) in the DNA backbone. SINGLE STRAND BREAK REPAIR: • Breaks in a single strand of the DNA molecule are repaired using the same enzyme systems that are used in Base-Excision Repair (BER).
  • 45. TYPES OF DSBs REPAIRS