Intracellular Recovery after Irradiation
165
inhibitors may markedly affect survival level. At the present time it appears
rather difficult to give a unified picture of all the effects found, nevertheless an
attempt will be made to design a concept based on recent experimental work.
Recovery effects at the cellular level have been studied from two points
of view, namely, recovery from so-called "sublethal" and from "lethal"
damage [16]. The first phenomenon is revealed by the split-dose technique,
the second leads to a modification of the survival curve. The term "recovery
from lethal damage" is not completely satisfactory, because it is by definition
impossible. We shall therefore prefer "recovery from potentially lethal
damage". Since the techniques involved, the systems tested and the questions arising are different with the two effects, they will at first be discussed
separately.
II. Recovery from Sublethal Damage
If the survival curve of an organism shows a shoulder, this fact may be
described by stating that a certain amount of damage has to accumulate before it becomes lethal, or, in other words, if the given dose does not reach this
level, it is sublethal. In terms of hit-theory: one hit is sublethal if the survival curve has a two-hit shape. The question is whether a surviving cell
which has suffered only sublethal damage is able to repair it. If this were
the case, cells having survived a first (usually called "conditioning") dose
should behave as nonirradiated cells when irradiated for a second time.
If the two dose-fractions are equal, each leaving a proportion p of surviving
cells, the surviving fraction after two irradiations is expected to be p2 if
complete recovery of sublethal damage has taken place between them. To
answer the question, ELKIND and SUTTON [10, 11] used the technique
described with Chinese hamster cells in culture: A dose of X-rays sufficient
to reach a survival level beyond the shoulder region of the survival curve
was split into two fractions spaced in time by variable intervals. They found
complete recovery if the time interval was sufficiently long, the cells being
kept in optimal medium between the dose fractions. This result has been
confirmed in the meantime for many other systems, e.g. yeast [3], plant
roots [31] and the intestinal crypt cells of mice [23]. The time needed for the
repair processes to be completed is of the order of the mitotic cycle time.
Fig. 1 shows the kinetics of recovery for diploid Saccharomyces cerevisiae from
early stationary phase cultures kept in glucose-yeast extract medium at
30° C between dose fractions. The peculiar shape of the curve is typical for
this process and found with almost every system tested. It depends, however, on the metabolic state of the cell as discussed below.
The early experiments of ELKIND and his group stimulated further work
in many laboratories, focussing interest on three main questions: 1. What
is the nature of the recovery process? 2. What is the reason for the particular
shape of the recovery curve? 3. How can it be modified?
165
inhibitors may markedly affect survival level. At the present time it appears
rather difficult to give a unified picture of all the effects found, nevertheless an
attempt will be made to design a concept based on recent experimental work.
Recovery effects at the cellular level have been studied from two points
of view, namely, recovery from so-called "sublethal" and from "lethal"
damage [16]. The first phenomenon is revealed by the split-dose technique,
the second leads to a modification of the survival curve. The term "recovery
from lethal damage" is not completely satisfactory, because it is by definition
impossible. We shall therefore prefer "recovery from potentially lethal
damage". Since the techniques involved, the systems tested and the questions arising are different with the two effects, they will at first be discussed
separately.
II. Recovery from Sublethal Damage
If the survival curve of an organism shows a shoulder, this fact may be
described by stating that a certain amount of damage has to accumulate before it becomes lethal, or, in other words, if the given dose does not reach this
level, it is sublethal. In terms of hit-theory: one hit is sublethal if the survival curve has a two-hit shape. The question is whether a surviving cell
which has suffered only sublethal damage is able to repair it. If this were
the case, cells having survived a first (usually called "conditioning") dose
should behave as nonirradiated cells when irradiated for a second time.
If the two dose-fractions are equal, each leaving a proportion p of surviving
cells, the surviving fraction after two irradiations is expected to be p2 if
complete recovery of sublethal damage has taken place between them. To
answer the question, ELKIND and SUTTON [10, 11] used the technique
described with Chinese hamster cells in culture: A dose of X-rays sufficient
to reach a survival level beyond the shoulder region of the survival curve
was split into two fractions spaced in time by variable intervals. They found
complete recovery if the time interval was sufficiently long, the cells being
kept in optimal medium between the dose fractions. This result has been
confirmed in the meantime for many other systems, e.g. yeast [3], plant
roots [31] and the intestinal crypt cells of mice [23]. The time needed for the
repair processes to be completed is of the order of the mitotic cycle time.
Fig. 1 shows the kinetics of recovery for diploid Saccharomyces cerevisiae from
early stationary phase cultures kept in glucose-yeast extract medium at
30° C between dose fractions. The peculiar shape of the curve is typical for
this process and found with almost every system tested. It depends, however, on the metabolic state of the cell as discussed below.
The early experiments of ELKIND and his group stimulated further work
in many laboratories, focussing interest on three main questions: 1. What
is the nature of the recovery process? 2. What is the reason for the particular
shape of the recovery curve? 3. How can it be modified?