4.2 Fundamental Principles of Radiobiology Flashcards
if the dose is delivered continuously but at a lower dose rate, it is
said to be _____
-When 6 Gyt is delivered at the rate of 10 mGyt/hr for a total time of 600
hours, the mouse will survive
protracted
If the 6-Gyt dose is delivered at the same dose rate, but in 12 equal fractions
of 500 mGyt, all separated by 24 hours, the mouse will survive. In this
situation, the dose is said to be _____
fractionated
Six gray (600 rad) delivered in 3 -minutes at a dose of 2 Gyt/min is \_\_\_\_ for a mouse
lethal
The response of biologic tissue to radiation is ____ when irradiated in the oxygenated, or aerobic, state than when irradiated in anoxic or hypoxic conditions.
greater
OER (oxygen enhancement ratio)=
OER= dose necessary under anoxic conditions to produce a given effect / dose necessary under aerobic conditions to produce the same effect
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.
oxygen enhancement ratio (OER)
It is theorized that
oxygen is needed in order for free radicals to form during ionization
of water. Without the free radicals, hydrogen peroxide is not formed,
and thus cell damage is _____
reduced
OER depends on ____
LET
The OER is most pronounced for ___
LET radiation, and is less effective with __ LET radiation
most - low,
less - high
Because of the physical differences between high and low LET radiation, the quantity of damage done by high LET radiation would
be beyond repair. Thus, having oxygen present would not _____
the response to radiation to the same magnitude, as would be the case with low LET radiation
intensify
Humans are most _____
before birth and are most
____ during
maturity
sensitive,
radioresistant
With old age, humans again tend to become more _____
radiosensitive
Tissue is more sensitive to radiation when irradiated in the oxygenated state than when irradiated under anoxic (without oxygen) or hypoxic (low-oxygen) conditions.
This characteristic of tissue radiation response is called
the _____ and is described numerically by the
_____
oxygen effect,
oxygen enhancement ratio (OER)
without oxygen
anoxic
low-oxygen
hypoxic
high-pressure
Hyperbaric
has been used in radiation oncology in an attempt to enhance the radiosensitivity of nodular, avascular tumors, which are less radiosensitive than tumors
with an adequate blood supply
Hyperbaric (high-pressure)
oxygen
The OER is highest for low-LET radiation, with a maximum value of approximately __ that decreases to approximately __ for high-LET radiation
3,
1
a decrease in the size of a tissue or organ due
to cellular shrinkage
cell atrophy
In vitro experiments show that if dose is not sufficient to induce interphase death, then cell will be able to _____
recover
occurs when the cell dies before replicating
Interphase death
At the whole-body
level, this recovery from radiation damage is assisted through _____ by surviving cells
repopulation
If a tissue or organ receives a sufficient radiation
dose, it responds by shrinking. This is called ____, and it occurs because some cells die and disintegrate,
and are carried away as waste products
atrophy
Recovery =
Recovery = Intracellular repair + Repopulation
agents that enhance the effect of radiation
Radiosensitizers
halogenated pyrimidines, methotrexate, actinomycin D, hydroxyurea,
and vitamin K
Radiosensitizers
become incorporated
into the DNA of the cell and amplify the effects of radiation on that molecule
halogenated pyrimidines
include molecules that
contain a sulfhydryl group (sulfur and hydrogen bound together), such as cysteine and cysteamine
Radioprotectors (Radioprotective compounds)
have not found human application because, to be effective, they must be administered at toxic levels. The protective agent can be worse than the radiation
Radioprotective agents
A separate and small body of radiobiologic evidence suggests that a
little bit of radiation is good for you
Hormesis
Interactions with Radiation
- Radiolysis of Water
- Irradiation of Macromolecules
- Single-Hit Chromosome Aberrations
- Multi-Hit Chromosome Aberrations
- Reciprocal Translocations
When an atom of water is irradiated this ionizes the water, and produces a free radical
Radiolysis of Water
an uncharged molecule that contains a single unpaired
electron in its outermost or valence shell, which makes it chemically unstable and highly reactive
Free Radical
Reactions of water include:
- H2O + radiation = HOH+ + e-
- H2O + e- = HOH–
- HOH+ = H+ + OH*
- HOH- = OH- + H*
- OH* + OH* = H2O2
- H* + O2 → HO*2
- HO2 + HO2 → H2O2 + O2
occurs when an atom has an extra electron, or has had an electron removed
Ionization
If an ion has more electrons than it does protons, it is designated with a _____ sign. If an ion has more protons than electrons, it is designated with a ____ sign
negative,
positive
The occurrence of molecular derangements or lesions may be classified as either effects on _____ or effects on _____
macromolecules,
water
If macromolecules are exposed to ionizing radiation ___, a significant dose
of radiation is needed to produce a measurable effect
in vitro
Irradiating macromolecules ___ shows that when cells
are in their natural conditions, they are much more radiosensitive
in vivo
The three primary effects of irradiating macromolecules in vitro include
main-chain scission, cross-linking, and point lesions
occurs when the thread
or backbone of the long-chain molecule is broken
Main-Chain Scission
This results in the long-chain molecule being reduced
to numerous smaller molecules, which can still be
macromolecular in nature. Not only is the size of the
macromolecule reduced, but its viscosity is also
reduced
Main-Chain Scission
Some macromolecules have small, spur-like side
structures that extend off the main chain. Others
produce these spurs as a consequence of irradiation
Cross Linking
Others develop these spurs after being irradiated.
After being irradiated, these spurs can act as if they had sticky material on their ends. These spurs can attach to neighboring macromolecules or to another segment of the same molecule. This stickiness causes the macromolecule to
connect to another macromolecule, or to another section of the same
molecule
Cross Linking
is increased by
radiation-produced molecular cross-linking
Viscosity
Radiation interaction with macromolecules also can
result in disruption of single chemical bonds,
producing ____
Point Lesions
may cause slight molecular changes,
which in turn cause the cell to function incorrectly
Point Lesions
At low doses of radiation, _____ are regarded to be the cellular
radiation damage that is responsible for the late radiation effects,
which are observed at the whole-body level
Point Lesions
are not detectable, but they can cause a minor modification of
the molecule, which in turn can cause it to
malfunction within the cell.
Point Lesions
its radiosensitivity is midway between that of DNA and protein macromolecules
RNA
These molecular genetic mutations are termed _____, and are common with low LET radiations
Point mutations
may be either of minor or major significance to the cell. A very major
effect of these point mutations would be the genetic code being
incorrectly transferred to daughter cells.
Point mutations
When chromosomes are irradiated, the interaction can be either direct or indirect. The result of either interaction is called a __
hit
Chromosome hits cause a
____ chromosome change. Such a hit would mean that numerous molecular bonds had been interfered with, and that several chains of DNA had been severed
visible
breakage of a chromatid
chromatid deletion
can occur in G1 phase and G2 phase of cell cycle
Single-Hit Chromosome Aberrations
During the S-phase of the cell cycle, the deletion and the remaining chromosome are replicated. The chromosome abnormality
that is seen during metaphase is a normal-appearing chromosome
with material missing from the ends of two sister chromatids and two
acentric fragments. Such fragments are called _____
isochromatids
There is a ___ probability that ionizing radiation will pass through
sister chromatids to produce isochromatids
low
A single chromosome can sustain more than one hit
Multi-Hit Chromosome
Aberrations
are not uncommon,
Multi-Hit Chromosome
Aberrations
During the G1 phase of the cell cycle, if two hits occur on one chromosome, _____ are produced
ring chromosomes
When neighboring chromosomes each suffer one hit and then recombine, this produces ____
dicentrics
a chromosome with two centers or two centromeres
dicentric
The quality of the _____ present at the severed chromosome is the determining factor for the joining of the chromatid
stickiness
During the __ phase of the cell cycle, similar chromosomal abnormalities can occur. These types of aberrations are rare, as they
require that the same chromosome is hit two or more times, or that
neighboring chromosomes are hit and join together
G2
are representative of major
cell damage
Multi-Hit Chromosome
Aberrations
are multi-hit chromosomal aberrations
Reciprocal translocations
If chromosomes experience this type of alteration, they do not lose
any genetic material, but instead the genes become rearranged. This
results in all genetic codes being available, but sequenced incorrectly
Reciprocal translocations
At the doses received in diagnostic radiology, only _____ types of chromosomal aberrations are seen
single-hit
If the radiation dose is not known, the approximate chromosomal aberration frequency will be:
-two single-hit aberrations/rad/1,000 cells,
-one multi-hit aberration/
10 rad/1,000 cells
