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cellular transformation or cell death
The response of the cell is either _______ or _______.
cellular transformation
______ can result in a late stochastic effect at the human level.
deterministic effect
Cell death can result in an early __________ at the human level.
recovery and repair metabolic processe
Most effects on cells result in no response because of _________ and ________.
Radiation damage
___________ to such a molecule could affect the cell severely because no similar molecules would be available as substitutes.
target theory
Radiation damage to such a molecule could affect the cell severely because no similar molecules would be available as substitutes. This concept of a sensitive key molecule serves as the basis for the _________. According to the _________, for a cell to die after radiation exposure, its target molecule must be inactivated
DNA
______ is the target molecule.
Cell Lethality
Originally, the target theory was used to represent _________.
Target Theory
It can be used equally well, however, to describe nonlethal radiation-induced cell abnormalities
target
In the target theory the ______ is considered to be an area of the cell occupied by the target molecule or by a sensitive site on the target molecule.
Target
This area changes position with time because of intracellular molecular movement.
randomly
The interaction between radiation and cellular components is _______; therefore, when an interaction does occur with a target, it occurs ________.
hit
When radiation does interact with the target, a ______ is said to have occurred.
hit
Radiation interaction with molecules other than the target molecule also can result in a _____
not possible
It is _________ to distinguish between a direct and an indirect hit.
Hits
______ occur through both direct and indirect effects
indirect effect
When a hit occurs through ________, the size of the target appears considerably larger because of the mobility of the free radicals.
indirect effect of radiation.
When a hit occurs through indirect effect, the size of the target appears considerably larger because of the mobility of the free radicals. This increased target size contributes to the importance of the__________
low
With low-LET radiation, in the absence of oxygen, the probability of a hit on the target molecule is ______ because of the relatively large distances between ionizing events.
free radicals
If oxygen is present, _______ are formed and the volume of effectiveness surrounding each ionization is enlarged. Consequently, the probability of a hit is increased
high
When high-LET radiation is used, the distance between ionizations is so close that the probability of a hit by direct effect is ______.
does not result in additional hits
When oxygen is added to the system and high-LET radiation is used, the added sphere of influence for each ionizing event, although somewhat larger, _________.
bacteria
Early radiation experiments at the cell level were conducted with simple cells, such as ________.
cell cloning
If normal cells are planted individually in a Petri dish and are incubated for 10 to 14 days, they divide many times and produce a visible colony that consists of many cells. This is ____________.
fewer colonies
A higher radiation dose leads to the formation of ____________.
cell survival
The lethal effects of radiation are determined by observing __________, not cell death.
two models
When a mathematical extension of target theory is used, ________ of cell survival result.
single-target, single-hit model
The _________ applies to biologic targets, such as enzymes, viruses, and simple cells such as bacteria.
multi-target, single-hit model
The _________ applies to more complicated biologic systems such as human cells.
Radiation
_______ interacts randomly with matter.
wasted radiation dose
Just as with the wet squares, however, as the dose increases, some cells will sustain two or more hits. All hits per target in excess of one represent _______ because the bacteria had been killed already by the first hit.
inactivates
A hit is not simply an ionizing event but rather an ionization that ______ the target molecule.
D37
______ is a measure of the radiosensitivity of the cell.
low D37
A ______ indicates a highly radiosensitive cel
high D37
a _______ reveals radioresistance.
100%
If there were uniform irradiation (no wasted radiation), D37 would be sufficient to kill ______ of
the cells.
N0
_____ is the initial number of cells,
D37
_______ is a constant dose related to cell radiosensitivity.
more than a single critical target
Complex biologic specimens such as human cells are thought to have __________
inactivated
Suppose that the human cell has two targets, each of which has to be _____ for the cell to die.
100%
At very low radiation doses, cell survival is nearly ______.
both target molecules
At very low radiation doses, cell survival is nearly 100%. As the radiation dose increases, fewer cells survive because more sustain a hit in ________
single-target, single-hit model
At a high radiation dose, all cells that survive have one target hit. Therefore, at still higher doses, the dose-response relationship would appear as the __________
D0
The ____ is called the mean lethal dose
D0
_______ is a constant related to the radiosensitivity of the cell. It is equal to D37 in the linear portion of the graph and therefore represents the dose that would result in one hit per target in the straight-line portion of the graph if no radiation were wasted.
large D0
A ______ indicates radioresistant cells.
small D0
A _____ is characteristic of radiosensitive cells.
target number
The extrapolation number is also called the _______.
2
The extrapolation number is also called the target number. When this type of experiment was first conducted with human cells, the observed extrapolation number was _____.
DQ
The ______ is called the threshold dose.
DQ
It is a measure of the width of the shoulder of the multi-target, singlehit model and is related to the capacity of the cell to recover from sublethal damage
DQ
large
A ______ DQ indicates that the cell can recover readily from sublethal radiation damage.
multi-target, single-hit model
The shoulder of the graph of the __________ shows that for mammalian cells, some damage must be accumulated before the cell dies
sublethal damage
The shoulder of the graph of the multi-target, single-hit model shows that for mammalian cells, some damage must be accumulated before the cell dies. This accumulated damage is called ________.
more sublethal damage
The wider the shoulder, the _______ that can be sustained and the higher the value of DQ.
DQ
_______ is a measure of the capacity to accumulate sublethal damage and the ability to recover from sublethal damage.
cell-cycle time
When human cells replicate by mitosis, the average time from one mitosis to another is called the __________.
24 hours
Most human cells that are in a state of normal proliferation have cell-cycle times of approximately _______
G1 phase
Longer cell-cycle times primarily result from lengthening of the ______ of the cell cycle.
G1
______ is the most time variable of cell phases.
synchronized
A randomly growing population of cells that are uniformly distributed in position throughout the cell cycle can be ________ in various ways.
M phase
Human cells are most radiosensitive in _____ and most radioresistant in late S.
late S phase
Human cells are most radiosensitive in M phase and most radioresistant in _______.
mitosis
Cells in ______ are always most sensitive.
mitosis
The fraction of surviving cells is lowest in this phase.
G1–S transition
The next most sensitive phase of the cell cycle occurs at the _______.
late S phase
The most resistant portion of the cell cycle is the ________.
oxygen
Mammalian cell survival experiments have been used extensively to measure the effects of various types of radiation and to determine the magnitude of various dose-modifying factors, such as ______
effectiveness of the dose modifier
D0, is related to radiosensitivity, the ratio of D0 for one condition of irradiation compared with another is a measure of the ___________, whether it is physical or biologic.
single-target, single-hit model
At very high LET (as with alpha particles and neutrons), cell-survival kinetics follow the ____________.
multi-target, single-hit model
With low-LET radiation (x-rays), the_______________ applies.
single-target, single-hit model
Irradiation of mammalian cells with high-LET radiation follows the ____________.
greater than
The mean lethal dose after low-LET irradiation is always _________ that after high-LET irradiation.
oxygen
The most completely studied dose modifier is __________.
oxygen
The presence of ________ maximizes the effect of low LET radiation
anoxic
When _______ cells are exposed, a considerably higher dose is required to produce a given effect.
high-LET radiation
With __________, little difference is noted between the response of oxygenated cells and that of anoxic cells.
target theory
The concept of a sensitive key molecule within a cell serves as the basis for the _____________.
DNA
For a cell to die after radiation exposure, the target molecule, ______, must be inactivated.
bacteria
The single-target, single-hit model applies to simple cells such as ________.
dose threshold
The multi-target, single-hit model implies a ________.
single-hit, single target model
at higher doses, the relationship becomes a _____________.
sublethal radiation damage
Experiments in cell recovery show that cells can recover from _______________.