Al-Azhar University-Gaza

Faculty of Dentistry

Radiation Biology
Biologic Effects of Ionizing Radiation
• Radiation biology
• Radiation biology is the branch of biology concerned with the effects
of ionizing radiation on living systems.
• Radiation Energy Transfer Determinants
• Characteristics of ionizing radiation vary among different types of
radiation.
• Characteristics include: (1) Charge (2) Mass (3) Energy
• To understand the way ionizing radiation causes injury and how the
effects can vary in biologic tissue, three important concepts must be
studied:
1. Linear Energy Transfer
2. Relative Biologic Effectiveness
3. Oxygen Enhancement Ratio
• Linear Energy Transfer (LET)
• LET describes a measure of the rate at which energy is deposited as
a charged particle travels through matter.
• LET is described in terms of keV/micrometer. LET is a function of the
physical characteristics of radiation, that is, mass and charge.
• The rate of transfer of energy from ionizing radiation used for
diagnostic purposes to soft biologic tissue is estimated to be 3
keV/µm.
• This is considered to be relatively low-LET radiation compared with
other types of radiation, which can have very much higher keV/µm
values.
• When LET increases, the chance of producing a significant biologic
response in the radiosensitive DNA macromolecule grows.
• Relative Biologic Effectiveness (RBE)
• Biologic damage produced by radiation intensifies as the LET of
radiation increases.
• RBE describes the relative capabilities of radiation with differing LETs
to produce a particular biologic reaction.
• RBE is a comparison of a dose of test radiation to a dose of 250 kVp
X-ray that produces the same biologic response.
• The RBE measures the biologic effectiveness of radiations having
different LETs.
• RBE is expressed as follows:
Dose in Gyt from 250-kVp x-rays (Reference Radiation)
RBE =
Dose in Gyt of test radiation
Note: Gray tissue (Gyt), unit used to measure the radiation quantity absorbed dose in tissue.
Example:
A biologic reaction is produced by 2 Gyt of a test radiation. It
takes 10 Gyt of 250-kVp x-rays to produce the same biologic
reaction.What is the RBE of the test radiation?
Answer:
Dose in Gyt from 250-kVp x-rays (Reference Radiation)
RBE =
Dose in Gyt of test radiation
10
5=
2
The RBE is 5, which means that the test radiation is five times
as effective in producing this biologic reaction as are 250-kVp
x-rays.
• Oxygen Enhancement Ratio (OER)
• When irradiated in an oxygenated, or aerobic state, biologic tissue is
more sensitive to radiation than when it is exposed to radiation
under anoxic (without oxygen) or hypoxic (low-oxygen) conditions.
This is known as the oxygen effect.
• The oxygen effect is described numerically by the oxygen
enhancement ratio (OER).
• OER is defined as the dose of radiation that produces a given
biologic response under anoxic conditions divided by the dose of
radiation that produces the same biologic response under aerobic
conditions.
• OER is expressed as follows:
Radiation dose required to cause biologic response without Oxygen
OER= Radiation dose required to cause biologic response with Oxygen

OER depends on LET. The OER is most pronounced for low LET
radiation, and is less effective with high LET radiation.
In general, x-rays and gamma rays, which are low-LET types of
radiation, have an OER of approximately 3.0 when the radiation dose
is high.
The OER for high LET radiations is between 1.2 and 1.7.
• Direct and Indirect Effects of Radiation
• When radiation interactions occur in a cell, these ionizations and
excitations develop either in macromolecules (such as DNA) or in their
suspension medium (such as water). Depending on the location of the
interaction is classified as either:
• Direct interaction is said to take place when an original ionizing
incident happens on that macromolecule (for example, DNA, RNA,
protein, or enzyme). If a macromolecule becomes ionized, it is considered
abnormal and thus damaged.
• Indirect interaction occurs if the initial ionizing incident takes place on
a distant noncritical molecule, which then transfers the ionization of
energy to another molecule.
• Radiolysis of Water
• Ionization of Water Molecules
• An interaction between an x-ray photon and a water molecule could
create an ion pair consisting of a water molecule with a positive
charge (HOH⁺) and an electron (e⁻).
• After the original ionization of the water molecule, several
reactions are possible.
1. The positively charged water molecule (HOH⁺) may recombine
with the electron (e⁻) to reform a stable water molecule (HOH⁺ +
e⁻ = H2O). If this happens, no damage will occur.
2. The electron (the negative ion) may join with another water
molecule to produce a negative water ion (H2O + e⁻ = HOH⁻).
• Production of Free Radicals
• The positive water molecule (HOH⁺) and the negative water
molecule (HOH⁻) are basically unstable. Hence they will break
apart into smaller molecules.
• HOH⁺ becomes a hydrogen ion (H⁺) and a hydroxyl radical (OH*),
whereas HOH⁻ becomes a hydroxyl ion (OH⁻) and a hydrogen
radical (H*).
• Hence the interaction of radiation with water results in the
formation of an ion pair, H⁺ and OH⁻ (hydrogen ion and hydroxyl
ion), and two free radicals, H* and OH* (a hydrogen radical and a
hydroxyl radical).
• Production of Cell-Damaging Substances
• Hydrogen and hydroxyl radicals are not the only destructive
substances produced during the radiolysis of water.
• A hydroxyl radical (OH*) can bond with another hydroxyl radical
(OH*) and form hydrogen peroxide (OH* + OH*= H2O2), a
substance that is very poisonous to the cell.
• In addition, a hydroperoxyl radical (HO2*) is formed when a
hydrogen free radical (H*) combines with molecular oxygen (O2).
This radical and hydrogen peroxide are believed to be among the
primary substances that produce biologic damage directly after the
interaction of radiation with water.
• Organic Free Radical Formation
• Absorption of radiation can cause a normal organic molecule (RH, in
which H stands for hydrogen and R can be any organic molecule) to form
the free radicals R* (an organic neutral free radical) and H*.
• Without oxygen, these radicals usually react with each other to reform
the original organic molecule (RH).
• When oxygen is present, however, R* and H* may react with oxygen
molecules (O2) to form the radicals RO2* and HO2
• Hence the original organic molecule (RH) is destroyed and replaced by
the radicals RO2* and HO2*.
• These radicals can react with other organic molecules to cause biologic damage.
Thus a small-scale chain reaction of destructive events results when radiation
deposits energy within tissue in the presence of oxygen.
• Indirect Action
• When free radicals previously produced by the interaction of
radiation with water molecules act on a molecule such as DNA, the
damaging action of ionizing radiation is indirect in the sense that the
radiation is not the immediate cause of injury to the macromolecule.
• The by-products of the radiation, the free radicals, are the immediate
cause of this damage.
• Because the human body is 80% water and less than 1 % DNA,
essentially all effects of irradiation in living cells result from indirect
action.
• Effects of Ionizing Radiation on DNA
• Single-Strand Break
• If ionizing radiation interacts with a DNA macromolecule,
the energy transferred could rupture one of its chemical
bonds and possibly sever one of the sugar phosphate
chain side rails, or strands, of the ladderlike molecular
structure (single-strand break).
• This type of injury to DNA is called a point mutation.
Such a single alteration along the sequence of nitrogenous
bases can result in a gene abnormality.
• Point mutations commonly occur with low-LET radiation.
• Repair enzymes, however, are often capable of reversing
this damage.
• Double-Strand Break
• Further exposure of the affected DNA macromolecule
to ionizing radiation can lead to additional breaks in the
sugar-phosphate molecular chain(s).
• These breaks may also be repaired, but double-strand
breaks (one or more breaks in each of the two sugar
phosphate chains) are not fixed as easily as single-strand
breaks.
• If repair does not take place, further separation may
occur in the DNA chains, threatening the life of the cell.
• Double-strand breaks occur more commonly with
densely ionizing (high-LET) radiation.
• Double-Strand Break in the Same Rung
of DNA.
• When two interactions (hits), one on each of
the two sugar-phosphate chains, occur within
the same rung of the DNA ladderlike
configuration, the result is a cleaved or broken
chromosome, with each new portion
containing an unequal amount of genetic
material.
• If this damaged chromosome divides, each
new daughter cell will receive an incorrect
amount of genetic material.
• This will culminate in either death or impaired
functioning of the new daughter cell.
• Mutation
• In general, the interaction of high energy radiation with a
DNA molecule causes a loss of or change in a
nitrogenous base on the DNA chain. The direct
consequence of this damage is an alteration of the base
sequence.
• Because the genetic information to be passed on to
future generations is contained in the strict sequence of
these bases, the loss or change of a base in the DNA
chain represents a mutation.
• It may not be reversible and may generate acute
consequences for the cell.
• if the cell remains viable, incorrect genetic information
will be transferred to one of the two daughter cells when
the cell divides.
• Covalent Cross-Links
• Covalent cross-links are chemical unions created between atoms by the single
sharing of one or more pairs of electrons.
• Cross-linking may happen between complementary DNA strands or between
entirely different DNA molecules. These joining are termed interstrand cross-
links.
• Crosslinking can occur between two places on the same
DNA strand. This joining is termed an intrastrand
cross-link.
• Finally, DNA molecules also may become covalently linked
to a protein molecule.
• All these linkages are potentially fatal to the cell if they
are not properly repaired.
• Effects of Ionizing Radiation on Chromosomes
• Radiation-Induced Chromosome Breaks
• Chromosomal Fragments.
• After chromosome breakage, two or more chromosomal fragments are
produced. Each of these fragments has a fractured extremity.
• These broken ends are chemically very active and therefore have a strong
tendency to adhere to another similar sticky end.
• The broken fragments can:
1. Rejoin in their original configuration
2. Fail to rejoin and create an aberration (lesion or anomaly)
3. Join to other broken ends and thereby create new chromosomes that
may not look structurally altered compared with the chromosome
before irradiation.
• Target Theory
• The target theory interprets the effect of radiations by direct hits on
sensitive cellular targets.
• The biologic effects of exposure to radiation stem primarily from the
ionizations occurring at sensitive cellular points secondary to energy
transfers from that radiation.
• These affected locations in a cell or, more specifically, on a vital molecule
within the cell are known as "targets.“
• Whether or not such locations are struck by radiation is a random
process. From all existing evidence, it appears that producing a serious
effect usually requires more than one radiation "hit" on a specific target.
The damage from a single hit normally is not conclusive because of repair
mechanisms.
• This concept of radiation damage resulting from discrete and random
events is known as target theory.
• The target theory holds
that the cell will die after
exposure to ionizing
radiation only if the master,
or key, molecule (DNA) is
inactivated in the process.

• A, An x-ray photon passes

through the cell without
interacting with the master
molecule, which is located in
the cell nucleus; no
measurable effect results.

• B, An x-ray photon enters

the nucleus and interacts
with and inactivates the
master molecule; the cell
dies as a result.