RADIATION, NUCLEAR AND NANO MEDICINES

BYT.R.DIVYA m.sc

Bharathidasan university

MY TOPIC

ISOTOPESRADIOISOTOPESRADIOACTVE DECAYHALF LIFEDIRECT AND INDIRECT ACTION OF RADIATIONRADIATION INDUCED DAMAGEREPAIR 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 neutronsHydrogen 2 : 1 proton and 1 neutronHydrogen 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.

RADIOISOTOPEDEFINITION: • 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 decayβ decayϒ decay

RADIOACTIVE DECAY

RADIOACTIVE DECAYα – 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 DECAYβ – 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 DECAYϒ – 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 DAMAGEINTRODUCTION:• 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 RADIATIONRADIATION 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.DepurinationB.Deamination of cytosine to uracilC.Deamination of adenine to hypoxanthineD.Alkylation of baseE.Insertion or deletion of nucleotideF.Base-analog incorporation

2 Two-base alterations A. UV light–induced thymine-thymine (pyrimidine) dimerB. Bifunctional Alkylating agent cross-linkage

3 Chain breaks A. Ionizing radiationB. Radioactive disintegration of backbone elementC. Oxidative free radical formation

4 Cross-linkage A. Between bases in same or opposite strandsB. 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

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