Intracellular Recovery after Irradiation
J. KIEFER
With 4 Figures
Abstract
Investigations on recovery from sublethal and potentially lethal damage in
cultured mammalian cells and microorganisms are reviewed and some new experimental results with yeast presented. The processes of recovery from sublethal and
potentially lethal damage are not necessarily qualitatively different although they
appear to be antagonistic in several repects. A model is developed, whose basic
features are: after irradiation two processes enter into competition, viz. damage
repair and damage fixation, both of which may be influenced differently by certain
treatments. The experimental results are discussed in terms of the model suggested.
I. Introduction
It is obvious that the manifestation of biologically significant damage
may take place at different levels in the hierarchy of organismic organisation.
At each of these levels reversions of the initial impact may occur. It seems
important for the sake of clarity to use a clearly defined terminology,
as suggested in a former paper [32] based on a scheme by BACQ and ALEXANDER [6].
Throughout this paper recovery will mean only those processes which
take place within the cell between the time of irradiation and the first subsequent cell division. A cell will be termed "lethally damaged" if it is not
able to form a macrocolony. The considerations to be presented will
be based mainly on work with mammalian cells in culture and microorganisms, for two reasons: 1. there are only a few data on organized systems,
and 2. systemic effects may obscure the cellular phenomena or interfere
with them in an unknown manner. In the classical hit-theory (d. e.g. [54])
the course of events was considered to be determined after the absorption
of the photon at the critical site. Shoulders in the survival curves were interpreted in terms of multi-hit or multi-target models. During the last decade,
however, evidence has accumulated to show that the initial lesion can be
modified in many respects after irradiation. One conclusion of these investigations bears out the importance of post-irradiation culture conditions.
Variations in temperature, nutrient medium or the application of metabolic
J. KIEFER
With 4 Figures
Abstract
Investigations on recovery from sublethal and potentially lethal damage in
cultured mammalian cells and microorganisms are reviewed and some new experimental results with yeast presented. The processes of recovery from sublethal and
potentially lethal damage are not necessarily qualitatively different although they
appear to be antagonistic in several repects. A model is developed, whose basic
features are: after irradiation two processes enter into competition, viz. damage
repair and damage fixation, both of which may be influenced differently by certain
treatments. The experimental results are discussed in terms of the model suggested.
I. Introduction
It is obvious that the manifestation of biologically significant damage
may take place at different levels in the hierarchy of organismic organisation.
At each of these levels reversions of the initial impact may occur. It seems
important for the sake of clarity to use a clearly defined terminology,
as suggested in a former paper [32] based on a scheme by BACQ and ALEXANDER [6].
Throughout this paper recovery will mean only those processes which
take place within the cell between the time of irradiation and the first subsequent cell division. A cell will be termed "lethally damaged" if it is not
able to form a macrocolony. The considerations to be presented will
be based mainly on work with mammalian cells in culture and microorganisms, for two reasons: 1. there are only a few data on organized systems,
and 2. systemic effects may obscure the cellular phenomena or interfere
with them in an unknown manner. In the classical hit-theory (d. e.g. [54])
the course of events was considered to be determined after the absorption
of the photon at the critical site. Shoulders in the survival curves were interpreted in terms of multi-hit or multi-target models. During the last decade,
however, evidence has accumulated to show that the initial lesion can be
modified in many respects after irradiation. One conclusion of these investigations bears out the importance of post-irradiation culture conditions.
Variations in temperature, nutrient medium or the application of metabolic