Transcript Slide 1

Basic Biologic Interactions of
Radiation
RADIOLYSIS OF WATER
Because the human body is an aqueous solution
that contains approximately 80% water
molecules, irradiation of water represents the
principal radiation interaction in the body. When
water is irradiated, it dissociates into other
molecular products; this action is called
radiolysis of water
When an atom of water (H2O) is irradiated, it is
ionized and dissociates into two ions—an ion
pair
The HOH and HOH− ions are relatively
unstable and can dissociate into still smaller
molecules
The final result of the radiolysis of water is the formation
of an ion pair, H+ and OH−, and two free radicals, H* and
OH*. The ions can recombine; therefore, no biologic
damage would occur
These types of ions are not unusual. Many
molecules in aqueous solution exist in a loosely
ionized state because of their structure. Salt
(NaCl), for instance, easily dissociates into Na+
and Cl− ions. Even in the absence of radiation,
water can dissociate into H+ and OH− ions.
A free radical is an uncharged
molecule that contains a single
unpaired electron in the outer shell.
Free radicals are unstable and therefore exist with
a lifetime of less than 1 ms. During that time,
however, they are capable of diffusion through the
cell and interaction at a distant site. Free radicals
contain excess energy that can be transferred to
other molecules to disrupt bonds and produce
point lesions at some distance from the initial
ionizing event
The H* and OH* molecules are not the only free
radicals that are produced during the radiolysis
of water. The OH* free radical can join with a
similar molecule to form hydrogen peroxide
Hydrogen peroxide is poisonous to the cell
and therefore acts as a toxic agent.
The H* free radical can interact with
molecular oxygen to form the hydroperoxyl
radical
The hydroperoxyl radical, along with hydrogen
peroxide, is considered to be the principal
damaging product after the radiolysis of water.
Hydrogen peroxide also can be formed by the
interaction of two hydroperoxyl radicals
Some organic molecules, symbolized as
RH, can become reactive free radicals
When oxygen is present, yet another
species of free radical is possible
Free radicals are energetic molecules
because of their unique structure. This
excess energy can be transferred to
DNA, and this can result in bond breaks.
When biologic material is irradiated in vivo, the
harmful effects of irradiation occur because of
damage to a particularly sensitive molecule, such
as DNA. Evidence for the direct effect of radiation
comes from in vitro experiments wherein various
molecules can be irradiated in solution. The
effect is produced by ionization of the target
molecule
If the initial ionizing event occurs on the target
molecule, the effect of radiation is direct
On the other hand, if the initial ionizing event occurs
on a distant, noncritical molecule, which then
transfers the energy of ionization to the target
molecule, indirect effect has occurred. Free
radicals, with their excess energy of reaction, are the
intermediate molecules. They migrate to the target
molecule and transfer their energy, which results in
damage to that target molecule.
The principal effect of radiation on
humans is indirect
It is not possible to identify whether a given
interaction with the target molecule resulted from
direct or indirect effect. However, because the
human body consists of approximately 80% water
and less than 1% DNA, it is concluded that
essentially all of the effects of irradiation in vivo
result from indirect effect. When oxygen is present,
as in living tissue, the indirect effects are amplified
because of the additional types of free radicals that
are formed
When one irradiates tissue, the response of the
tissue is determined principally by the amount of
energy deposited per unit mass—the dose in rad
(Gyt). Even under controlled experimental
conditions, however, when equal doses are
delivered to equal specimens, the response may not
be the same because of other modifying factors. A
number of physical factors affect the degree of
radiation response
Linear energy transfer (LET) is a measure of the
rate at which energy is transferred from ionizing
radiation to soft tissue. It is another method of
expressing radiation quality and determining the
value of the radiation weighting factor (WR)
used in radiation protection . LET is expressed in
units of kiloelectron volt of energy transferred per
micrometer of track length in soft tissue (keV/μm).
The ability of ionizing radiation to produce a
biologic response increases as the LET of
radiation increases. When LET is high,
ionizations occur frequently, increasing the
probability of interaction with the target
molecule.
As the LET of radiation increases, the ability
to produce biologic damage also increases.
This relative effect is quantitatively
described by the relative biologic
effectiveness (RBE).
The standard radiation, by convention, is
orthovoltage x-radiation in the range of 200 to 250
kVp. This type of x-ray beam was used for many
years in radiation oncology and in essentially all
early radiobiologic research.
Diagnostic x-rays have an RBE of 1. Radiations with
lower LET than diagnostic x-rays have an RBE less
than 1, whereas radiations with higher LET have a
higher RBE.
Type of Radiation
LET (keV/μm)
RBE
25 MV x-rays
0.2
0.8
gamma rays 0.3
0.9
60Co
1 MeV electrons
0.3
0.9
Diagnostic x-rays
3.0
1.0
10 MeV protons
4.0
5.0
Fast neutrons
50.0
10
5 MeV alpha
particles
100.0
20
Heavy nuclei
1000.0
30
Question: When mice are irradiated with 250
kVp x-rays, death occurs at 650 rad (6.5 Gyt). If
similar mice are irradiated with fast neutrons,
death occurs at only 210 rad (2.1 Gyt). What is
the RBE for the fast neutrons?
If a dose of radiation is delivered over a long period
of time rather than quickly, the effect of that dose is
lessened. Stated differently, if the time of irradiation
is lengthened, a higher dose is required to produce
the same effect. This lengthening of time can be
accomplished in two ways.
If the dose is delivered continuously but at a lower
dose rate, it is said to be protracted. Six hundred
rad (6 Gyt) delivered in 3 min (200 rad/min [2
Gyt/min]) is lethal for a mouse. However, when 600
rad is delivered at the rate of 1 rad/hr (10 mGyt/hr)
for a total time of 600 hr, the mouse will survive
If the 600 rad dose is delivered at the same dose
rate, 200 rad/min, but in 12 equal fractions of 50
rad (500 mGyt), all separated by 24 hr, the mouse
will survive. In this situation, the dose is said to be
fractionated
Dose protraction and fractionation cause less
effect because time is allowed for intracellular
repair and tissue recovery.