4.1 Fundamental Principles of Radiobiology Flashcards by Dana Athena Augusto

refers to the breakdown of a cell caused by damage to its membrane

lysis

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process that results in an increase of the number of cells

cell proliferation

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enlargement of an organ or tissue caused by an increase in the
amount of organic tissue that results from cell proliferation

hyperplasia

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outside the body or cell

in vitro

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inside the living cell

in vivo

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experimented on rodent testicles to observe the effects of radiation

Jean Alban Bergonié and Louis Tribondeau (1906)

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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.

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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)

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The testes were selected because they contain both ____

mature and immature cells

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mature cells

spermatozoa

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execute the

organ’s principal function

mature cells (spermatozoa)

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immature cells

spermatogonia and spermatocytes

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evolve into mature, functional cells

The immature cells (spermatogonia and spermatocytes)

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The ______ cells divide frequently, whereas the ______ cells
do not divide

spermatogonia,

spermatozoa

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After irradiating the testes, _______

noticed the immature cells were injured at lower doses than the mature cells

Jean Alban Bergonié and Louis Tribondeau (1906)

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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

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This law concludes that compared to a child or mature adult, the
fetus is most radiosensitive

Law of Bergonie and Tribondeau

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modified the

law of Bergonie and Tribondeau

Paul Ancel and P. Vitemberger (1925)

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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

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Ancel and Vitemberger theorized that the most significant biologic stress on the cell is the need for ______

cell division

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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)

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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

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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

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original ionization occurs directly on target

molecule

direct effects

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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

RBE of 10 MeV protons

RBE of Fast Neutrons

RBE of 5 MeV alpha particles

RBE of Heavy nuclei

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