Download DNA Strand Breaks and Chromosomal Aberration II-Radiation Biology-Lecture Slides and more Slides Radiation Biology in PDF only on Docsity! Radiation induced anaphase bridge
type chromosomal aberrations in
Radiation induced translocation &
deletion type chromosomal
aberrations
broken pieces are exchanged between the two
chromosomes, and the “sticky” ends rejoin. This
aberration is not necessarily lethal to the cell
There are examples in which an exchange
aberration of this type leads 10 the activation of
an oncogene. See Chapter 10 on radiation
carcinogenesis, B: Diagram af a deletion.
Radiation produces two breaks in the same arm
of the same chromosome. What actually
happens is illustrated more clearly in Figure 2.10.
FIGURE 2.9 @ A; Formation of a symmetric
translacation, Radiation produces breaks in two
different prereplication chromosomes. The —-
Effects of radiations at molecular
level
The various macromolecules in the
cellular structures are:
« Carbohydrates
- Proteins
« Lipids (fatty acids)
Effects of radiations on
carbohydrates
A carbohydrate is an organic compound
consists only of carbon, hydrogen, and
oxygen,
The carbohydrates (saccharides) are divided
into four chemical groupings:
monosaccharides, disaccharides,
oligosaccharides, and polysaccharides
For example, blood sugar is the
monosaccharide glucose
Primary direct action of radiation on ;
carbohydrate is chain breakage, degradation,
decreased viscosity. H—C—_O
Maile sugars in at aa in the
absence of oxygen, results in polymer
ease This may be attributed to cross- CH oC
inking
Effects of radiations on proteins
s Proteins are biochemical compounds consisting of one or more
polypeptides typically folded into a globular or fibrous form,
facilitating a biological function.
ms Aminoacids join togather to form a protein by successive coupling on
amino and carboxylic groups with the elimination of water molecule.
= The eligi! of energy by IR leads to structural changes in the
form o
- Hydrogen bond breakage
¢ Molecular degradation
¢ Intramolecular or intermolecular cross-linking
Effects of radiations on cell
membrane
¢ Radiation induced changes in the
electrical activity of nerve indicates an
increase in passive ion permeability of
thye nerve axon.
¢ Similarly following 30 Gy dose,
microvilli in the epithelial cells of
mammalian intestine swells and
eventually burst & bloted
Effects of radiations on
lysosomes
- According “enzyme release hypothesis”, following
radiation induced membrane damage, the
unplanned release of enzyme occurs inside the cell
and causes its death.
« Such increased permeability of lysosomal
membrane and 5-6 fold increase in lysosomal
enzyme activity can be detected in spleen and
thymus cells within 1-3 hours of 8.5 Gy of ©°Co,
(ere laal ante oN AS
- The free lysosomal enzymes are capable of
damaging proteins, polysaccharides and lipids
Effects of radiations on ER
- ER is a system of membranes that run throughout
the cytoplasm and to which many enzyme systems
are attached, These enzymes require an intact
membrane for full activity.
« When membrane of ER is damaged by radiation,
enzyme activity is impaired. Secondly, ribosomes
are attached to the ER system and it is on
ribosomes that the mRNA code is translated., into
the a acid sequence, giving a specific protein
molecule. Radiation damage to the ER may reduce
the protein synthesis
Radiation effect on DNA synthesis &
division delay
« G, Blockage seems to be due to interference with
the chromatine condensation process that is
essential for the formation of mitotic chromosomes
and this occurs when DNA is in close association
with the nuclear envelope
- It is difficult to summarize the post —irradiation
depression in DNA Synthesis because
it is not dose dependent But also depend on the
phase of the cycle at which radiation is given. For
example, In one cell line 5 Gy given to cells in
mitosis caused 70% reduction in DNA synthesis
while same dose (5Gy) given to G, cells produced
only 20 deficiency in DNA
Radiation effect on DNA synthesis &
division delay
« It means that mitosis & G,/S border
are the most sensitive phases
¢ It is concluded that division delay
leads to delay in DNA synthesis and
overall reduction in the amount od
DNA synthesis. Deficient DNA
synthesis leads to RNA synthesis and
so deficient of essential proteins
Nuclear damage Vs Cytoplasmic
in following IR
Q: Is it possible to kill cell, if only cytoplasm or
only nucleus is irradiated?
A: As majority of informations reside in the
nucleus as genetic code in DNA so it is
expected that any damage to nucleus will
be of primary importance whereas damage
to cytoplasm will be of secondary
importance.
T support the answer some experiments can
be perormed.