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Chapter 7
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What is Radiation Biology?
Molecular & Cellular Radiation Biology
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A branch of biology concerned with how
ionizing radiation effects living systems.
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Biological damage that occurs from
different types of ionizing radiation
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Charge, mass, and energy vary among
different types of ionizing radiation
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Ionizing Radiation
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Energy Transfer Determinants
Removing electrons from an Atom.
This ionized Atom will not bond properly
in molecules.
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LET – Linear Energy Transfer
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RBE – Relative Biological Effectiveness
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OER – Oxygen Enhancement Ratio
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Linear Energy Transfer (LET)
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A method of expressing radiation quality.
kiloelectron volts (keV) per micron (1 micron [µm]
=10-6 m)
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A measure of the rate at which radiation energy is
transferred to soft tissue (track).
An important factor in assessing tissue and organ
damage from exposure to ionizing radiation.
Low-LET/High-LET
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Low-LET: x-rays – electron shells. Gamma rays short-wavelength, high-energy waves emitted by
the nuclei of radioactive substances
High-LET: particles that possess substantial mass
and charge (alpha particles, ions of heavy nuclei,
low-energy neutrons, and charged particles
released from interactions between neutrons and
atoms).
Dense ionization along the length of the track.
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Low LET
Low LET
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It does not relinquish all of its energy
quickly.
Indirect action from free radicals
Less destructive to biological matter.
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High LET
High LET
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Particles with mass and charge
Dense ionization along the track. More
ionization per unit of distance traveled.
Lose energy more rapidly
More destructive to biological matter.
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LET
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Low LET vs. High LET
Low LET
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More penetration
Less destruction to
biological matter
Gives up less energy
(less interaction)
Less ionizing
Electromagnetic radiation
Indirect action
High LET
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Less Penetration
More destruction to
biological matter
Gives up more energy
(more interaction)
More ionizing
Particle radiation
Direct action
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Relative Biologic Effectiveness
(RBE)
Relative Biologic Effectiveness
(RBE)
As LET increases the ability to produce
biological damage also increases.
Radiations with different LETs will
produce different biological effects.
RBE is used for specific experiments
with specific cells or animal tissues.
It is not used for radiation protection
doses in humans.
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RBE - Example
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The relative biological effectiveness for
a given test radiation, is calculated as
the dose of a reference radiation
(usually x-rays) required to produce the
same biological effect as was seen with
a test dose, DT, of another radiation.
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RBE
If it took 200 mGy of x rays but only
20mGy of neutrons to produce the
same biological effect, the RBE would
be 200/20 = 10 using x rays as the
reference radiation.
Which means:
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 The
20 mGy of neutrons is 10 times as
effective in producing the biological
reaction as the 200 mGy of x-ray.
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For radiation protection purposes, the
International Commission on
Radiological Protection, ICRP, has
described the effectiveness of radiations
of differing qualities by a series of
Quality Factors (ICRP 1977) and more
recently by a series of Radiation
Weighting Factors (ICRP 1991).
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Oxygen Enhancement Ratio
(OER)
Radiation Weighting Factors
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http://www.hps.org/publicinformation/ate/q647.html.
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OER
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OER
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OER describes the sensitivity of
oxygenated tissue mathematically by
dividing the dose necessary under
anoxic conditions to produce a given
effect by the dose necessary under
aerobic conditions to produce the same
effect.
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High LET (direct action) – presence or
absence of oxygen is of no
consequence
Low LET (predominately indirect action)
– the presence of oxygen makes the
damage caused by free radicals
permanent (the oxygen fixation
hypothesis)
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Molecular Effects
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Direct/Indirect Action
Direct Hit – an x-ray photon hits a
critical molecule and damages or kills it
(DNA)
Indirect Hit – an x-ray photon hits a
water molecule and produces a free
radical that hits a critical molecule and
damages or kills it (DNA)
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INDIRECT HIT THEORY
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Radiolysis of H2O molecule
Shared electron
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Water to Hydrogen peroxide
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(And kill indirectly)
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Shared electron
H-O-H  HOH+ + e- (ionization)
95% of cellular damage
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Module Medical VIII.
(free radicals)
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Radiolysis of H2O molecule
Free Radicals
Shared electron
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Shared electron
H-O-H  HOH+ + e- (ionization)
H-O-H+  H+ +OH0
(free radicals)
Module Medical VIII.
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Configuration of one or more atoms that
have an unpaired electron but no
electrical charge.
Free radicals are formed by the rupture
of a bond in a stable molecule with the
production of two fragments, each with
an unpaired electron. The resulting free
radicals may participate in further
reactions or may combine to reform the
original compound.
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Reactions with free radicals
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Target Theory
OH0 + OH0  H2O2 (hydrogen peroxide)
O2 + H0  HO20 (hydroperoxl) Radical
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This free radical and hydrogen peroxide
are among the primary substances that
produce biological damage directly
after interaction of water and radiation.
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Master molecule is responsible for the
survival of the cell.
DNA is the master molecule.
Destruction of the master molecule
results in cell death.
Takes more than one hit.
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Cellular Effects of Irradiation
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Radiosensitive Cells
Instant death (1000 Gy)
Reproductive death (1-10 Gy)
Apoptosis, or programmed cell death
(interphase death)
Mitotic, or genetic, death
Mitotic delay (0.01 Gy)
Interference of function
Chromosome breakage
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Radioinsensative Cells
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Nerve Cells
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Muscle Cells
Lymphocytes
Erythroblasts
Cancer cells
Spermatogonia
Crypt cells of the small intestine
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Cell Sensitivity
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System sensitivity
Oxygen Enhancement Effects
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If a cell type in a system is sensitive, then
Oxygen increases radio sensitivity.
Why would a patient undergoing
radiation therapy treatments also have
hyperbaric treatments?
the entire system is sensitive
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Radiosensitivity
Law of Bergonie & Tribondeau
RADIOSENSITIVITY is a function of:
 Metabolic state of the cell
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Differentiation: most mature or
specialized. (inversely proportional)
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Reproductive rate (directly proportional)
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Least mature
Least specialized
Highly reproductive
Longest mitotic phase
What cells qualify?
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Lympocytes
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Nerve Tissue
Leukocytes refers to white blood cells.
Lymphocytes refers to a subgroup.
Provide protection from antigens.
Lymphocytes produced in bone marrow
are the most radiosenstive blood cell in
the human body.
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In adults less radiosensitve than in the
embryo-fetus stage.
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Adult single dose of 50Gy may lead to
death within a few hours or days.
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Nerve Tissue
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Reproductive cells
Radiosensitve during the embryo-fetus
stage of development
Window of maximal sensitivity 8-15
weeks after gestation.
Lower risk from this stage through 25
weeks.
After 25 weeks risk not found to be
significantly different from that of young
adults.
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Radiosensitive.
Irradiation can cause depression to sterility in
men.
Dose as low as 0.1Gy in a male could
depress sperm count or cause genetic
mutations in future generations.
Dose of 5Gy in women can cause sterility in
woman.
Women 20-30 exhibit the lowest degree of
sensitivity
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Questions?
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