lec369vvvvvvvvvvvvvvvvvvvvvvvvvvvvvv5.ppt

lec369vvvvvvvvvvvvvvvvvvvvvvvvvvvvvv5.

2. 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, damage occurs as 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 damage on the key
molecule results in a biologic effect.

3. Ionization of atoms in molecules is a result
of absorption of energy by photoelectric
and Compton interactions. Ionization
occurs at all radiation qualities but is the
predominant cause of damage in
reactions involving high LET radiations.
Absorption of energy sufficient to remove
an electron can result in bond breaks.
 Ionizing radiation+RH R
-
+ H
+

4. 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.

5. 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 (H
2
)
2.The formation of toxic hydrogen peroxide (H
2O
2).
3.The radical can also be transferred to an organic
molecule in the cell.
H-O-H  H OH
+
+ e (ionization)
H OH
+
+ e H
0
+OH
0
(free radicals)

6. H
0
+ OH
0
HOH (recombination)
H
0 +
H
0
 H
2 (dimer)
OH
0
+

OH
0
 H
2
O
2
(peroxide dimer)
OH
0
+ RH  R
0
+ 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
H
0
+O
2
 HO
2
0
(hydroperoxy free radical)
R
0
+O
2
RO
2
0
(organic peroxy free radical)

7. The lifetimes of simple free radicals (H
0
or OH
0
)
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.

8. 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 peroxy free radical can transfer
the radical form molecule to molecule
causing damage at each encounter. Thus a
cumulative effect can occur, greater than a
single ionization or broken bond.

9. 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.
The DNA molecule takes the form of a twisted
ladder or double helix. The sides of the ladder
are strands of alternating sugar and phosphate
groups. Branching off from each sugar group is
one of four nitrogenous bases: cytosine,
thymine, adenine and guanine.
I I
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

10. There is considerable evidence
suggesting that DNA is the primary target
for cell damage from ionizing radiation.
Toxic effects at low to moderate doses
(cell killing, mutagenesis, and malignant
transformation) appear to result from
damage to cellular DNA. Thus, ionizing
radiation is a classical genotoxic agent.

11. The lethal 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.

12. Residual unrejoined double strand breaks
are lethal to the cell, whereas incorrectly
rejoined 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.

13. 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.

14. After irradiation, chromosomes may appear to be
"sticky" with formation of temporary or permanent
interchromosomal bridges preventing normal
chromosome separation during mitosis and
transcription of genetic information. In addition,
radiation can cause 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 or abnormal nuclei.

15. 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 structure can cause changes in its
permeability to various molecules, i.e., electrolytes. In
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)

16. DNA- mutation:Unusual permanent change in
the primary structure of DNA ( gene mutation).
Chromosomal mutation: change in the amount
of DNA in chromosomes (aberrations) leads to
abnormalities in cell division.
 Genotoxic:damging the genetic information

17. MARK [T] FOR TRUE AND [F] FOR FALSE
STATEMENTS FROM THE FOLLOWING.(correct
the false statement):
Drugs in aqueous media are generally more
stable to radiation than in dry state?
Free radicals, regardless of how they are
formed, are chemically less active than neutral
atoms.?

18. Ionization occurs at all radiation qualities but is
the predominant cause of damage in reactions
involving low LET radiations.?
 The lifetimes of simple free radicals (H
0
or OH
0
)
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?
 

19. The oxygen derived species such as hydroperoxy
free radical does not readily recombine into
neutral forms. These less stable forms have a
lifetime long enough to migrate to the nucleus
where serious damage can occur.?
 There is a considerable evidence suggesting that
RNA is the primary target for cell damage from
ionizing radiation.?
 

20.  Ionizing radiation has been suggested as playing a
role in plasma membrane damage, which may be an
important factor in cell death or mutagenic effect ?
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.?
 

21. What are the temporal stages of radiation
action?
What are the products of water radiolysis?
What is the difference between direct and
indirect effects of radiation?