Radiobiology deals with the effects of radiation on living cells and tissues. Ionizing radiation can directly damage DNA through breaking bonds. It can also indirectly damage DNA through production of reactive oxygen species like hydroxyl radicals from radiolysis of water. High linear energy transfer (LET) radiation causes dense ionization over short tracks, making DNA damage harder to repair than low LET radiation. Relative biological effectiveness (RBE) compares the dose of different radiations needed for the same biological effect. The oxygen enhancement ratio (OER) represents increased radiation effect in oxygenated versus hypoxic tissues due to reactive oxygen species.

1. Presented by- Aaditya Sinha
M.Sc Radiotherapy Technology
SMS Medical College, Jaipur

2. OBJECTIVES
 To understand the radiobiological background of
radiotherapy.
 To be familiar with the cellular effects of radiation.
 To be aware of basic radiobiological terms like LET
(Linear Energy Transfer), RBE( Radiobiological
Effectiveness), OER (Oxygen Enhancement Ratio).

3. INTRODUCTION
 Radiobiology, in general terms, is the science
that evaluates the effects of radiation in living
organisms.
•The aim of radiotherapy is to
kill tumor cells - they may be in
a bulk tumor, in draining lymph
nodes and/or in small
microscopic spread.
•Tumor radiobiology is complex
- the response depends not only
on dose but also on individual
radiosensitivity, timing, fraction
size

4. Radio-Biology basically deals with the
effect of radiation at cellular level.

5.  CELLULAR EFFECTS OF
RADIATION
Ionizing radiation injects energy into a
meterial as it passes through it, and deliers
its energy in the medium until it is totally
absorbed.
Living cells commonly consist of long
chains, and some of these molecules can be
broken by exposing the cells in radiation.
The molecular fragments can then re-bond
in various ways, resulting in new
molecules.
These molecules cannot work like the
original molecules, and so they need to be
repaired.
These defective molecular structures will
accumulate in the cell, changing the cells
metabolism; if the defective molecule is
DNA.

6.  Although all molecules can be damaged
by radiation, DNA molecules that carry
genetic information related to cell
division and growth are most probable
targets.
 Radiation may damage or change a small
part of DNA helix. The damage is
repaired in most cases; but cell death
(Apoptosis) or transformation is
observed in some circumstances, and this
may result in malign transformations
and cause cancer.

7. Ionizing radiation can cause breaking,
sticking, clamping and curbling the
chromosomes.
Broken chromosomes can reorganize,
remains the same, or combine with other
chromosomes.
All of these events result in mutations or in
eventual cell death.

8. Direct effect of radiation at molecular level
 Radiation directly affects DNA molecules in the target
tissue. The direct ionization of atoms in DNA molecules
is the result of energy absorption via the Photoelectric
effect and Compton interactions.
 If this absorbed energy is sufficient to remove electrons
from the molecule, bonds are broken, which can break
one DNA strand or both.
 A single broken strand can usually be repaired by the
cell, while two broken strands commonly result in cell
death.
When normal cell DNA is damaged by radiation
provided in the kinds of doses normally used in
radiotherapy, the cell cycle is stopped by protein p53.The
DNA cannot be repaired, the cell then re-enters the cell
cycle and continues to proliferate.
If the DNA cannot be repaired, the cell enters
Apoptosis- Programmed Cell Death.
At high radiation doses, the molecules utilized by the
DNA repair mechanisms are damaged, so repair is not
possible, so repair is not possible, the cell loses its ability
to divide, and it subsequently dies.
What do
we meant
by direct
effect of
radiation?

9. A quarter to a third of the damage produced in cellular macromolecules by
radiation is due to its direct effect. This means most of the damage is produced by
the indirect effect of radiation.
Damage to cellular proteins following irradiation at biologically relevant doses
appears to be of relatively minor importance.

10. Indirect effect of radiation at molecular level
 The indirect effect of radiation on molecules
includes the formation of free radicals by
energy transfer from radiation, and resulting
molecular damage caused by the interaction
of free radicals with DNA.
 This phenomenon is most probably due to
interaction of radiation with water molecules,
since the human body is approximately 70%
water.
 Free radicals are electrically neutral atoms
that contain “free” electrons. They are highly
electrophilic and reactive.

11.  Water (H20) is ionized when exposed to
radiation, and has H2O H2O + e-, a
positively charged water molecule and a free
electron are formed.
 This free electron (e-) interacts with other
water molecule in the reactions: e- +H2O
H2O- , resulting in the formation of
negatively charged water molecule .
These charged water molecules undergoes the
reaction H2O+  H+ + OH- and
H2O-  H + OH- , yielding H+ and OH-
ions.
 These H and OH free radicals may combine
with other free radicals or with other
molecules. If the LET of the radiation is high,
the free OH- radicals do not combine with the
H+ radicals, and so they do not form H20.
 They combine with each other in the reactions
OH- + OH+  H20 2 and H+ + H+  H2, ,
forming Hydrogen Peroxide and hydrogen gas
molecules.
 Free radicals formed by
the hydrolysis of water
affect DNA.
The negative effect of
hydrogen peroxide on cell
nutrition may be employed
as evidence of indirect
effect of radiation.

12. Simple free radicals (H or OH) have very short lifetimes (10-10 s), and this time
span is too short for them from the cytoplasm to the nucleus, where the DNA is
located.
Therefore H combines with O2 and transforms into a more potent and lethal
free radical with a longer lifetime, called Hydrogen Peroxide (HO2).
Hygrogen peroxide, has an even longer lifetime 10-3 sec., it cannot move from
one place to another. It oxidizes the surroundings of the cells close to where it is
formed, and prevents nutrition of the neighbouring tissues or cells .
 This results in cell death through nutritive deficiency or the isolation of these
cells from other tissues.
.
So that’s what
indirect effect
means !!

13. Linear energy transfer (LET) is the energy transferred per
unit length of the track.
 Unit : kiloelectron volt per micrometer (keV/μm)of unit density material.
 LET can be only an average quantity because at the microscopic level, the energy per
unit length of track varies over such a wide range that the average has very little
meaning.
The biological effects of ionizing radiation depend on factors such as the characterstics of the
radiation and the target .
•Factors modifying biological effects of ionizing
radiation
Characteristics of radiation
The potential harm to biological materials caused by their irradiation is directly
proportional to the efficacy with which the radiation deposits energy in the material.
Proton, Neutron and Alpha particles lose their energies over much shorter distances than
X-Rays and Gamma rays with same energy.

14.  1- High LET Radiation
 2- Low LET Radiation
Types of LET (Linear Energy Transfer)
 This is a type of ionizing radiation that
deposit a large amount of
energy in a small distance.
 Eg. Neutrons , alpha particles
This is a type of ionizing radiation that
deposit less amount ofenergy along the
track or have infrequent or widely spaced
ionizing events.
 Eg. x-rays, gamma rays
High LET Radiation Low LET Radiation
Types Of Radiation LET (keV/μm)
Cobalt-60 0.3
250 kVp X-ray 2.0
10 Mev protons 4.7
150 Mev protons 0.5

15. High LET radiation ionizes water into H
and OH radicals over a very short
track. In fig. two events occur in a single cell
so as to form a pair of adjacent
OH radicals that recombine to form peroxide,
H2O2, which can produce
oxidative damage in the cell
Low LET radiation also ionizes water
molecules, but over a much longer
track. In fig. two events occur in separate
cells, such that adjacent radicals
are of the opposite type: the H and OH
radicals reunite and reform H2O.
High LET Radiation & Low LET Radiation

16. Comparison Between High LET Radiation and Low LET
Radiation
High-LET radiations are more destructive to
biological material
than low-LET radiations.
 The localized DNA damage caused by dense
ionizations from high-LET radiations is more
difficult to repair than the diffuse DNA damage
caused by the sparse ionizations from low-LET
radiations.
High LET radiation results in lower cell
survival per absorbed dose than low LET
radiation.
High LET radiation is aimed at efficiently killing
tumor cells while
minimizing dose to normal tissues to prevent
toxicity.
 Biological effectiveness of high LET radiation is
not affected by the time or stage in the life cycle of
cancer cells, as it is with low LET radiation.

17. Graph Between High LET Radiation and Low LET
Radiation

18. RBE ( Relative Biological Effectiveness)
RBE can be defined as the
biological damage produced by
same dose of different
radiations is not the same.
The dose required by 250
kVp X-rays to produce certain
biological effect, to the dose
required by the reference
radiation to produce same
effect.
The RBE depends upon the
linear energy (LET) of the
radiation in the medium.
The LET is the energy
transferred by the radiation
per unit path length
The National Bureau of Standards in
1954 defined RBE as:
◦ The RBE of some test radiation (r)
compared with x-rays is defined by the
ratio D250/Dr, where D250 and Dr are,
respectively, the doses of x-rays and the
test radiation required
for the equal biologic effects.
RBE = Dose from standard radiation to produce a given biological effect
----------------------------------------------------------------------------
Dose from test radiation to produce the same biological effect

19. Graphical representation between LET and RBE

20. Oxygen Enhancement Ratio
Soluble oxygen in tissues increases the stability the toxicity of free radicals. The
increase in the effect of radiation after oxygenation is defined as the Oxygen
Enhancement Ratio (OER)
 The maximum value of OER is 3. oxygenation can modify the indirect
effect of free radicals.
However, the OER plays no role in the direct effect of high LET
radiation; OER is 1 in this case.
Tumor become less hypoxic during fractionated radiation schedules.
OER = Required Dose under hypoxic conditions
--------------------------------------------------------------------------
Required dose under oxygenated conditions

21. OER as a function of LET
At low LET (x- or y-rays)
with OER between 2.5
and 3, as the LET
increases, the OER falls
slowly until the LET
exceeds about 60
keV/μm, after which the
OER falls rapidly and
reaches unity by the
time the LET has reached
about 200keV/μm.

22. OER and RBE as a function of LET
•The rapid increase in RBE and
the rapid fall of OER occur at
about the same LET 100keV/μm .
•Two curves are virtually mirror
images of each other.