Modeling of DNA damages
induction under ionizing radiation
of various qualities
Nermeen Kamel Abe El Moniem
Laboratory of Radiation Biology, JINR
Supervised by
Dr. Oleg Belov
Why is it Important to Calculate the
Yield of DNA Damages?
Yield of
DNA
damages
Output (Results)
•Input1
Model of
DSB repair
*Reaction
Rates k1,…, kn
Initial
Concentrations
of proteins
xo,yo,zo
*
Model of
SSB repair
• Input2
Model of
SOS system
…
Calculation of
concentration
change
output
Calculation
of mutation
frequency
…
DNA Damage
Damages at some specific locations can lead to
either cell death, or mutation or carcinogenesis.
Calculation of DNA Damage
 Models
of radiation damage in DNA can give at
least a qualitative insight as to the yields of such
damages and their dependence on radiation
quality.

The approach presented here comes from a
knowledge of


Structure of DNA
Radiation Track Structure
DNA Structure
There are four different types of nucleotides (monomer units)
found in DNA, differing only in the nitrogenous base. The four
nucleotides are
A adenine G guanine C cytosine T thymine nucleotides.

Track Structure


Track Structure is microscopic distribution of
energy
Geometrical pattern of energy deposition
around the trajectory of an incident particle.
Interaction of Ionizing Radiation With DNA
Direct Effect of Radiation :
Energy can be deposited directly on the
DNA molecule, creating ionized and
excited states of the various molecules
(sugar, bases, phosphates, etc.).
These physical processes can also lead to
DNA damage and are generally known as
the direct effects of radiation
Interaction of Ionizing Radiation With DNA
Indirect Effect of Radiation :
It has been demonstrated experimentally that
the products of water due to radiation
interaction can indirectly cause biochemical
changes in a DNA molecule and this process is
called the indirect affect of radiation damage
Assumptions of the Model
 This
model is based on the assumption that the
distribution of damage to DNA follows the
distribution of ionizing events within the molecule
and its surroundings.
 The damage due to direct effect is due to energy
deposition directly in a DNA molecule.
 The damage due to the indirect effect is
supposed to be caused by *OH radicals
produced in the water sheath around the DNA
molecule containing bound water.
 base ionization is equally probable to the
ionization of the sugar phosphate backbone
because electron densities of both are nearly the
Calculations
The calculation of DNA damage is based on
probability yi(j) that a cluster of j ionizations will
result in a damage of the i th type (where i th type
stands for type of break).
the Calculation is given by:
j
1
m
yi ( j)   Pov ( j, m) POH ( m, k) Pi ( j  m, k)
m 0 k 0
We need to calculate
Pov ( j, m)
POH (m, k)
Pi ( j  m, k)
PovP(ovj,(m
j, )m)
The calculation of probability of having m ionizations out of the
DNA and j-m within it if the cluster overlaps the DNA.
j 
j m
m
(
V
(
x
)
/
V
)
(
1

(
V
(
x
)
/
V
))
xdx


O
O

 m
 
x
Pov ( j, m)  j minx max
j 
j m
m
(
V
(
x
)
/
V
)
(
1

(
V
(
x
)
/
V
))
xdx



O
O

 m
m  0 x min 

x max
the cluster overlaps the DNA
x
We need to calculate area of
sphere without this part.
V(x) - volume of a given
distance x of the center of
cluster from DNA where cluster
represented by a sphere of
parameter equal to cluster
parameter p
POH (m, k)
Probability that m ionizations will result in k OH* radicals
reacting with DNA.
 m  1 
m 1
POH ( m, k )     G ( m)(1  G ( m))
1 k  1  k 
k
1 k
( DNA ) (1   DNA )
m
G(m) is the yield of OH* radicals per one ionization when m ionizations of given
cluster is in water sheath around DNA.
ρDNA is the probability that 'OH radical escaping scavenging will react with
DNA
Pi ( j  m, k)
Probability that j-m ionizations within DNA and k OH*
radicals reacting with DNA (both have origin in the
same cluster) will result in the ith type of damage .
Pi ( j  m, k ) 
 j1  m1 a  b 

  (s1 (SSB  SD ))C (s2 (SSB  SD ))bc


a 0 b 0 c 0  a
 b  c 
( b1 ( BSB   BD ))a  b ( b 2 ( BSB   BD ) j m1a )
j1 m1 a
b
 k  d  e 
   (sOH 1 (SSB  SD ))f (sOH 2 (SSB  SD ))ef

d  0 e  0 f  0  d  e  f 
( bOH 1 ( BSB   BD ))d e ( bOH 2 ( BSB   BD ) k d )
k
d
e
Variables

Now let us consider n ionizations in DNA molecule.

s1 = s2 = 0. 25 are the probabilities for one ionization
in DNA to cause damage to the sugar phosphate
backbone on the first (s1) or on the second (s2 )
strand.

b1 = b2 = 0. 25 are the respective probabilities for
one ionization in DNA to cause base damage.

ρBSB=0.67 is the probability that damaged sugar will
result in ssb . ρSD = 1 - ρSSB,

ρBSB = 0.1 is the probability that damaged base
cause ssb and ρBD = 1- ρBSB.

SOH1=SOH2=0.1 is the probabilities for one OH radical
to cause damage to the sugar-phosphate moiety
on the first SOH1or on the second (SOH2) strand.
Results
The calculations were performed for the
following types of DNA damages:
Damage probability 1y(j)
Results
Multiple strand break on one strand
SSB + damaged opposite strand
Single strand break
Double strand break
Cluster order j
Conclusion
• An algorithm for calculation of the
yield of different types of DNA
damages was realized in Wolfram
Mathematica package.
• The probability of DNA damages of
various types was calculated in
dependence on order of the cluster
formed after the ionization in DNA.
Future task
This work is released under the joint project between
laboratory of Radiation Biology and Cairo University.
This work will be continued.
Let Ni be the yield of damages of the i th type per unit of deposited
energy, then
Ni   h( j)(( j)1yi ( j)  (1  ( j))2 yi ( j))
j
Where h(j) is the cluster distributions.
For every type of radiation the probability ( j) that the cluster is
isolated (i.e. there are no neighbor clusters within the distance of
cluster parameter.
Ni is the value which we need to calculate next.
Thank You for Your Attention