Modifiers of Cell Survival: Repair. Modifiers of Cell Survival: Repair. Sub-lethal damage repair Half-time of repair Potentially lethal damage repair Effect of dose, dose rate, and cell type Effect of dose fractionation Effect of LET
Cell cycle not in progress
Cell cycle in progress
In neither case, there is dramatic dip in the curve at 6 hours resulting from movement of cells through the cell cycle, because the cell cycle is long
The mouse tumor data show more repair in small 1-day tumors than in large hypoxic 6-tumors
Half-time of repair
As the time interval between the two dose fractions is increased, there is a rapid increase in the fractions of cells surviving due to the prompt repair of sublethal damage.
The half-time of sublethal damage repair in mammalian cells is about 1 hour, but it may be longer in late-responding normal tissues in vivo.
Effect of dose fractionation
Multiple small fractions approximate to a continuous exposure to a low dose rate
Because continuous low-dose rate irradiation may be considered to be an infinite number of infinitely small fractions, the survival curve under these conditions also would be expected to have no shoulder and to be shallower than for single acute exposures
Survival curves for HeLa cells exposed to -rays at high and low dose rates
As the dose rate is reduced, the survival curve becomes shallower tends to disappear (I.e., survival curve becomes an exponential function of the dose)
The dose rate effect caused by SLD is most dramatic between 1-100 rad/min. Above or below this dose-rate range, the survival curve changes little.
Dose-response curves for Chinese hamster cells (CHL-F line) exposed to cobalt 60-g-rays at various dose rates.
The decrease in cell killing becomes even more dramatic as the dose rate is reduced further
and low dose rate (LDR)
The survival curves fan out at LDR because of the presence of a range of repair times for SLD and further is associated with a range of inherent radiation sensitivities
Response of mouse jejunal crypt cells irradiated with -rays.
There isa dramatic dose-rate effect owing to the repair of sub-lethal radiation damage from acute exposure of 274 rad/min to a protracted exposure at 0.92 rad/min.
Cell division dominates at LDR because the exposure time is longer than the cell cycle time.
Decreasing the dose-rate from 154 rad to 37 rad/h increases the efficiency of cell killing, which is as effective as an acute exposure.
The shoulder is present for X-rays suggesting the presence of SLD repair, whereas, in response to neutrons there is no shoulder suggesting loss of SLD repair.
Cell-survival curves for Chinese hamster cells at various stages of the cell cycle
From Sinclair W.K., Radiat Res. 33:620-643, 1968. The broken line is
a calculated curve expected to apply to mitotic cells under hypoxia.
of various oxygen concentrations. Oxygen is introduced gradually
into the biologic system.
The introduction of
a very small quantity
of oxygen, 100 ppm,
is readily noticeable
in a change in the
slope of the survival
A concentration of
2,200 ppm, which is
about 0.25% oxygen,
moves the survival
toward the fully