4.1 Fundamental Principles of Radiobiology Flashcards
refers to the breakdown of a cell caused by damage to its membrane
lysis
process that results in an increase of the number of cells
cell proliferation
enlargement of an organ or tissue caused by an increase in the
amount of organic tissue that results from cell proliferation
hyperplasia
outside the body or cell
in vitro
inside the living cell
in vivo
experimented on rodent testicles to observe the effects of radiation
Jean Alban Bergonié and Louis Tribondeau (1906)
Law of Bergonie and Tribondeau
- Stem or immature cells are more radiosensitive than
mature cells. - Younger tissues and organs are more radiosensitive than
older tissues and organs. - The higher the metabolic cell activity, the more radiosensitive
it is. - The greater the proliferation and growth rate for tissues, the
greater the radiosensitivity.
suggested that the intrinsic susceptibility of
damage to any cell by ionizing radiation is identical but timing of manifestation of radiation-produced damage varies according to cell type
Paul Ancel and P. Vitemberger (1925)
The testes were selected because they contain both ____
mature and immature cells
mature cells
spermatozoa
execute the
organ’s principal function
mature cells (spermatozoa)
immature cells
spermatogonia and spermatocytes
evolve into mature, functional cells
The immature cells (spermatogonia and spermatocytes)
The ______ cells divide frequently, whereas the ______ cells
do not divide
spermatogonia,
spermatozoa
After irradiating the testes, _______
noticed the immature cells were injured at lower doses than the mature cells
Jean Alban Bergonié and Louis Tribondeau (1906)
Supported by their observations, Bergonie and Tribondeau proposed a law
describing radiation sensitivity for all body cells. Their law maintains
that actively mitotic and undifferentiated cells are most susceptible
to damage from ionizing radiation
Law of Bergonie and Tribondeau
This law concludes that compared to a child or mature adult, the
fetus is most radiosensitive
Law of Bergonie and Tribondeau
modified the
law of Bergonie and Tribondeau
Paul Ancel and P. Vitemberger (1925)
Paul Ancel and P. Vitemberger experiments on mammals demonstrated that there are two factors that affect the manifestation
of radiation damage to the cell:
- The amount of biologic stress the cell receives
- Pre- and post-irradiation conditions to which the cell
is exposed
Ancel and Vitemberger theorized that the most significant biologic stress on the cell is the need for ______
cell division
They determined that a given dose of radiation will cause the same degree of damage to all cells, but only if and when the cell divides will damage be demonstrated
Paul Ancel and P. Vitemberger (1925)
Even though Ancel and Vitemberger convey radiosensitivity differently than Bergonie and Tribondeau, they do agree with them by
placing a significant emphasis on the amount of _____ activity
involved
mitotic
In the 1920s, researchers learned that the process of ionization in tissues was the cause of biologic results. The two mechanisms recognized were:
• Direct ionization along charged particle tracks caused direct
effects
• The formation of free radicals caused indirect effects
original ionization occurs directly on target
molecule
direct effects
original ionization occurs with water and transfers ionization to target molecule
indirect effects
In the early days of radiation, it was generally held that the biggest
dose (tolerated), given as ____ as possible, was the best treatment
fast
During the period, roughly 1920 to 1930, ______ argued
that the differential effect of X-rays on cancer and normal tissues
could be best obtained by giving the treatment slowly.
Claude Regaud
For example,
healing was very much better when skin cancer was treated over a
period of a week than in one day
Fractionation Theory
experimented on sheep testicles and found that if original dose was
fractionated into smaller doses spread over a period of time, animals would be
sterile but with considerably less damage to their skin
Claude Regaud
It was found that if the original dose was fractionated, or broken up into smaller doses spread out over a period of
time, the animals would still become sterile, but with considerably less
damage to their skin. Regaud called this the _____
Fractionation Theory
Extension of a total dose over a period of time (in days or weeks), in order to
minimize unwanted radiation effects on normal tissue
Fractionation Theory
argued that the differential effect of X-rays on cancer and
normal tissues could be best obtained by giving the treatment slowly
Claude Regaud
refers to the ability of normal tissues to
replenish themselves following injury.
Repopulation
is defined as the time during which a course of radiation is given
Protraction
The logic is that by protracting a course of radiation therapy of _____, one allows for
hyperplastic compensation in some critically affected normal tissues.
five to six weeks
Although it is likely that no increase in tolerance will be obtained
unless the protraction is extended to a period longer than _____,
some benefit may be obtained from this.
four weeks
The reason for the _____ requirement is that it may take this long for damaged cells to
die, to go through the process of lysis, thereby creating a local depletion of cells; and for the remaining cells to mount a replacement
proliferation. It is also likely that the tumor cells will continue to
proliferate throughout this period
four-week
discovered that ionizing radiation produced mutations
through his experiment with fruit flies
Herman Muller (1927)
He found that the radiation-induced mutations were the same as those
produced in nature. Irradiating the fruit flies did not create any
unusual effects, but the frequency of mutations was intensified.
Herman Muller (1927)
This implies that the effects of ionization were not unique to radiation;
that is, they could have been caused by things other than radiation.
Muller’s finding is termed _______
mutagenesis
determined oxygen to be a radiosensitizer because it increases the cell-killing effect of a given dose of radiation
Charles Rick
This occurs as a result of the increased production of free radicals when ionizing radiation is delivered in the presence of oxygen. This was named the _____
oxygen effect
did extensive research on the hydrolysis
of water with the resulting liberation of free radicals.
D. Lea (1946)
D. Lea termed his
finds the mechanism of ____
indirect action
experimented with the root tips of Vicia faba, discovered that the frequency of chromosome aberrations produced by X-rays depends on the amount of oxygen present during irradiation
John Read and John Thoday (1947)
exposed human uterine
cervix cells to varying doses of radiation.They experimentally determined
reproductive failure by counting the number of colonies formed by these
irradiated cells
Theodore Puck and Phillip Marcus (1956)
doing cancer research
using irradiated Chinese hamster cells, discovered the ability of cells to
recover from small radiation doses
Mortimer Elkind and H. Sutton-Gilbert (1959)
Cells are distinguished by their rate of proliferation and their stage of development
Radiosensitivity
known as undifferentiated, precursor, or stem cells
Immature cells
Cells that are considered highly radiosensitive include:
lymphocytes, spermatogonia, erythroblasts, and intestinal crypt cells
Cells that have an intermediate radiosensitivity include:
endothelial cells, osteoblasts, spermatids, and fibroblasts
Cells that have low radiosensitivity include:
muscle and nerve
cells, and chondrocytes
depends upon what part of the cell cycle the
cell is in
Cell radiosensitivity
are judged the most radiosensitive phases of the cell cycle
Mitosis, and the passage from late G1 into early S-phase
is considered to be the most radioresistant cell cycle
phase
Mid- to late S-phase
Numerous experiments have determined that the _____ of a cell is considerably more radiosensitive than is the cytoplasm of the cell
nucleus
is the most radiosensitive part of the cell
DNA
its radiosensitivity
is intermediate between that of DNA and protein
RNA
Chromosome-produced radiation damage can be analyzed during the _____
portion of the cell cycle
metaphase
order of radiosensitivity
DNA> RNA> protein
When a cell is irradiated,
three events may occur:
division delay, interphase
death, and cell death
It has been proven in experiments that low doses of radiation delay cell mitosis in humans. The specific cause for this slow-down,
known as ______, is unknown
division delay
cell death before entering mitosis which depends on which cell is irradiated
Interphase death
Highly mitotic cells demonstrate interphase death at doses ____ than cells that are not highly mitotic
lower
It is theorized that when there is a change in the cell membrane,
electrolytes become _____
imbalanced
The consequence for cells that do not divide repetitively, or that divide numerous times resulting in
dead cells being produced, is failure of ______
cell reproduction
When noting biologic changes that occur in cells caused by irradiating them, the following should be emphasized:
-Radiation interaction with cells has to do with chance and
probability.
-The first deposit of radiation is given very rapidly, approximately
within 10^-17 seconds.
-The interaction of radiation within the cell is random.
-It cannot be determined if visible changes to cells, tissues, and
organs are caused by radiation or other sources.
-Radiation doses to cells cause biologic changes only following a
period of time that is dose dependent, and may vary from minutes to years
Factors that affect
Radiosensitivity
- Physical Factors
- Biologic Factors
Factors that affect
Radiosensitivity
-Physical Factors
- Linear Energy Transfer
- Relative Biologic Effectiveness
- Protraction and Fractionation
Factors that affect
Radiosensitivity
-Biologic Factors
- Oxygen Effect
- Age
- Recovery
- Chemical Agents
The factors affecting cell response include:
- linear energy transfer (LET)
- relative biologic effectiveness (RBE)
- oxygen enhancement ratio (OER).
is a measure of the rate at which energy is deposited as a charged particle travels through matter, and is described in
terms of keV/µm
Linear Energy Transfer (LET)
another method of expressing radiation quality and determining the value of radiation weighing factor (W)
Linear Energy Transfer (LET)
ability to induce biologic response _____ as LET increases
increases
electromagnetic radiation produce few and sparse interactions because of their
fast-moving electrons (which have negligible mass and a –1 charge), is regarded as ___ LET radiation
low
particulate radiation which are highly ionizing
and have substantial mass and/or charge, are more likely to interact with tissue. These radiations lose their energy quickly, and produce numerous ionizations within a very short distance, is considered ___ LET radiation
high
is a function of the physical characteristics of radiation, that is, mass and charge
Linear Energy Transfer (LET)
x- and gamma-rays
electromagnetic radiation
alpha particles and neutrons
particulate radiations
The higher the LET of radiation, the _____ the chance for a
biologic interaction
greater
LET of 25 MV x-rays
0.2 keV/µm
LET of Cobalt-60 gamma rays
0.3 keV/µm
LET of 1 MeV electrons
0.3 keV/µm
LET of Diagnostic x-rays
3 keV/µm
LET of 10 MeV protons
4 keV/µm
LET of Fast Neutrons
50 keV/µm
LET of 5 MeV alpha particles
100 keV/µm
LET of Heavy nuclei
1000 keV/µm
RBE of 25 MV x-rays
0.8
RBE of Cobalt-60 gamma rays
0.9
RBE of 1 MeV electrons
0.9
RBE of Diagnostic x-rays
1
RBE of 10 MeV protons
5
RBE of Fast Neutrons
10
RBE of 5 MeV alpha particles
20
RBE of Heavy nuclei
30
The relative effect of LET is quantitatively described by the
relative biologic effectiveness (RBE)
is a comparison of a dose of test radiation to a dose of 250 keV X-ray that produces the same biologic response
relative biologic effectiveness (RBE)
measures the biologic effectiveness of radiations having different LETs
relative biologic effectiveness (RBE)
The constant is the _____, not the radiation dose.
biologic response
RBE=
RBE= Dose of standard radiation necessary to produce a given effect / Dose of test radiation necessary to
produce the same effect
Factors that influence RBE include:
radiation type, cell or tissue
type, physiologic condition, biologic result being examined, and the
radiation dose rate
In comparing LET and RBE, as LET increases, RBE ______
increases
The ability of ionizing radiation to produce a biologic response increases as the LET of radiation _____
increases
When LET is ____, ionizations occur frequently, increasing the probability of interaction with the target
molecule
high
The standard radiation, by convention, is ____ in the range of ____
orthovoltage x-radiation,
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
orthovoltage x-radiation
