 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.
 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+
 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.
 H-O-H  H OH+ + e (ionization)
H OH+ + e H0+OH0 (free radicals)
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 (H2)
2.The formation of toxic hydrogen peroxide (H2O2).
3.The radical can also be transferred to an organic
molecule in the cell.
 H0 + OH0 HOH (recombination)
 H0 + H0  H2 (dimer)
 OH0 + OH0  H2O2 (peroxide dimer)
 OH0 + RH  R0 + 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
 H0+O2  HO20 (hydroperoxy free radical)
 R0+O2 RO20 (organic peroxy free radical)
 The lifetimes of simple free radicals (H0 or OH0)
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.
 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.
I I
S-AT-S
 DNA is the most important material making up
the chromosomes and serves as the master
I I
P P blueprint for the cell. It determines what types of
I I RNA are produced which, in turn, determine the
S-CG-S types of protein that are produced.
I I  The DNA molecule takes the form of a twisted
P P ladder or double helix. The sides of the ladder are
I I strands of alternating sugar and phosphate groups.
S-GC-S Branching off from each sugar group is one of
I I four nitrogenous bases: cytosine, thymine, adenine
P P and guanine.
I I
S-TA-S
I I
 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.
 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.
 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.
 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.
 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.
 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)
 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
 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.?
 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 (H0 or OH0)
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?
  
 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.?
  
 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.?
  
 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?