Radiation Effects on DNA and Chromosomes by Y0W512G

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									Radiation Effects on DNA and
Chromosomes
So, what do you understand by DNA anyway?
DNA can be described as a long fiber that
resembles a hair under a powerful microscope.
The only difference is that they are much
thinner and longer. The whole structure is
made of two strands that are intertwined
together. When cells get ready to divide,
proteins attach themselves to the DNA and
leads to the creation of a chromosome.
Because the human body is an
aqueous solution that contains 80%
water molecules, radiation
interaction with water is the principal
radiation interaction in the body.
However, the ultimate damage
occurs to the target molecule, DNA,
which controls cellular metabolism
and reproduction.
The effect of irradiation of macromolecules is
quite different from that of irradiation of water.
When macromolecules are irradiated in vitro, that
is, outside the body or outside the cell, a
considerable radiation dose is required to produce
a measurable effect. Irradiation in vivo, that is,
within the living cell, demonstrates that
macromolecules are considerably more
radiosensitive in their natural state.
In vitro is irradiation outside of the cell
or body. In vivo is irradiation within the
body.
IRRADIATION OF MACROMOLECULES
A solution is a liquid that contains dissolved
substances. A mixture of fluids such as water
and alcohol is also a solution. When
macromolecules are irradiated in solution in
vitro, three major effects occur:
1. main-chain scission
2. cross-linking
3. point lesions
Main-chain scission is the breakage of the backbone of
the long-chain macromolecule. The result is the reduction
of a long, single molecule into many smaller molecules,
each of which may still be macromolecular.
Main-chain scission reduces not only the size of the
macromolecule but also the viscosity of the solution. A
viscous solution is one that is very thick and slow to flow,
such as cold maple syrup. Tap water, on the other hand,
has low viscosity. Measurements of viscosity determine
the degree of main-chain scission.
Cross-Linking
Some macromolecules have small, spur-like side
structures that extend off the main chain. Others
produce these spurs as a consequence of irradiation.
These side structures can behave as though they had
a sticky substance on the end, and they attach to a
neighboring macromolecule or to another segment of
the same molecule. This process is called cross-
linking. Radiation-induced molecular cross-linking
increases the viscosity of a macromolecular solution.
Point Lesions
Radiation interaction with macromolecules also can
result in disruption of single chemical bonds,
producing point lesions. Point lesions are not
detectable, but they can cause a minor modification
of the molecule, which in turn can cause it to
malfunction within the cell.
At low radiation doses, point lesions are
considered to be the cellular radiation damage
that results in the late radiation effects
observed at the whole-body level
Main scission   Cross-linking   Point lesions
Laboratory experiments have shown that all
these types of radiation effects on
macromolecules are reversible through
intracellular repair and recovery.
Radiation Effects on DNA
DNA is the most important molecule in the
human body because it contains the genetic
information for each cell. Each cell has a nucleus
that contains DNA complexed with other
molecules in the form of chromosomes.
Chromosomes therefore control the growth and
development of the cell; these in turn determine
the characteristics of the individual
The DNA molecule can be damaged without
the production of a visible chromosome
aberration. Although such damage is
reversible, it can lead to cell death. If enough
cells of the same type respond similarly, then a
particular tissue or organ can be destroyed.
Damage to the DNA also can result in abnormal
metabolic activity. Uncontrolled rapid proliferation
of cells is the principal characteristic of radiation-
induced malignant disease. If damage to the DNA
occurs within a germ cell, then it is possible that
the response to radiation exposure will not be
observed until the following generation, or even
later.
RADIATION RESPONSE OF DNA

• Main-chain scission with only single strand break
• Main-chain scission with double strand break
• Main-chain scission and subsequent cross-linking
• Base damage
Single strand   Double strand
                                Cross-linking   Base damage
   break           break
Single strand break


• Most likely efficiently repaired, with little, if
  any , long term consequences to the cell.
Double strand break
• Difficult for the cell to repair. They show
  reasonable corelaiton with cell killing. If
  repair does not take place, the DNA
  chains can separate, with serious
  consequence to the life of the cell.
Cross-linking
• Between two regions of the same DNA
  strand
• Between two complementary DNA strands
• Between two completely different DNA
  molecules
• Between DNA and protein

• Important if not repaired
Base damage
• The loss or a change of a base on the
  DNA chain results in the alteretion of the
  base sequence. Base sequence stores
  and transmits genetic information. It has
  nmajor consequences. Loss or change of
  base is considered a type of mutation.
The DNA molecule can be damaged without the
production of a visible chromosome aberration.
Although such damage is reversible, it can lead
to cell death. If enough cells of the same type
respond similarly, then a particular tissue or
organ can be destroyed
When radiation interacts with chromosomes, the
interaction can occur through direct or indirect
effect. In either mode, these interactions result in
a hit. The hit, however, is somewhat different
from the hit described previously in radiation
interaction with DNA.
The DNA hit results in an invisible disruption of
the molecular structure of the DNA. A
chromosome hit, on the other hand, produces a
visible derangement of the chromosome.
Because the chromosomes contain DNA, this
indicates that such a hit has disrupted many
molecular bonds and has severed many chains of
DNA
The study of chromosome damage from
radiation exposure is called cytogenetics
A chromosome hit represents severe
damage to the DNA.
The single-hit chromosome aberrations
The multi-hit chromosome aberrations
The multi-hit chromosome aberrations represent
rather severe damage to the cell. At mitosis, the
acentric fragments are lost or are attracted to only
one of the daughter cells because they are
unattached to a spindle fiber. Consequently, one
or both of the daughter cells can be missing
considerable genetic material.
Radiation-induced reciprocal translocations result in
no loss of genetic material, simply a rearrangement
of the genes. Consequently, all or nearly all genetic
codes are available; they simply may be organized
in an incorrect sequence.

								
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