Intracellular Recovery after Irradiation
173
for the second exposure will not be the same after different times of treatment. It appears unavoidable that this kind of investigation should have
sets of differently treated controls. Fixation apparently does not occur-or
at a very low rate-under LHR-or photoreactivation conditions. Thus,
these techniques appear useful for further investigations of the cellular
processes involved in recovery from radiation impact.
V. Biochemical Considerations
It is not intended to treat this matter here in detail as it is beyond the
scope of this lecture. Let me just set some spotlights which, I hope, are
relevant to our discussion. There are many indications that DNA is the
main target of radiation attack at the cellular level. It has, as everybody
knows, two purposes in the cell, to serve as initial template for messenger
RNA-synthesis and to replicate its own structure in order to preserve the
genetic information. Nearly all post-irradiation treatments which favour
recovery inhibit or delay DNA-synthesis, so that it has been proposed that
damage fixation is related to DNA replication [52]. It has been found that
initiation of DNA replication is connected with the breakage of hydrogen
bonds in the helix [46]. This effect might also be brought about by radiation,
so that the suggestion of an X-ray induced "S-phase" [30] appears plausible
and might partly account for the shape of the recovery curve in split-dose
experiments. DNA suffers degradation after X-irradiation (cf. e.g. [24]),
but not in minimal medium [1]. This might be an indication of the validity of
the explanation offered.
Recovery may take place as a normal part of RNA-synthesis. It may
involve so-called "repair-replication" which is not semi-conservative, as
proved by density-labelling experiments [43]. Recovery is certainly dependent on the energy metabolism of the cell. This fact fits very well into the
picture of "repair-replication", as very recent biochemical investigations
show that enzymes mediating the rejoining of open DNA-strands need
ATP or NAD as cofactors [40, 50]. The inhibition of recovery from sublethal damage by actinomycin D [12] of of LHR by DNA-complexing dyes
[42] also favours this hypothesis.
Conclusions
Obviously we are far from a real understanding of cellular recovery
processes. All the models discussed give no more than hypotheses for certain aspects. The interesting feature is the hope that we can obtain by these
studies not only radiobiological knowledge but also a deeper insight into
the normal functioning of the cell.
173
for the second exposure will not be the same after different times of treatment. It appears unavoidable that this kind of investigation should have
sets of differently treated controls. Fixation apparently does not occur-or
at a very low rate-under LHR-or photoreactivation conditions. Thus,
these techniques appear useful for further investigations of the cellular
processes involved in recovery from radiation impact.
V. Biochemical Considerations
It is not intended to treat this matter here in detail as it is beyond the
scope of this lecture. Let me just set some spotlights which, I hope, are
relevant to our discussion. There are many indications that DNA is the
main target of radiation attack at the cellular level. It has, as everybody
knows, two purposes in the cell, to serve as initial template for messenger
RNA-synthesis and to replicate its own structure in order to preserve the
genetic information. Nearly all post-irradiation treatments which favour
recovery inhibit or delay DNA-synthesis, so that it has been proposed that
damage fixation is related to DNA replication [52]. It has been found that
initiation of DNA replication is connected with the breakage of hydrogen
bonds in the helix [46]. This effect might also be brought about by radiation,
so that the suggestion of an X-ray induced "S-phase" [30] appears plausible
and might partly account for the shape of the recovery curve in split-dose
experiments. DNA suffers degradation after X-irradiation (cf. e.g. [24]),
but not in minimal medium [1]. This might be an indication of the validity of
the explanation offered.
Recovery may take place as a normal part of RNA-synthesis. It may
involve so-called "repair-replication" which is not semi-conservative, as
proved by density-labelling experiments [43]. Recovery is certainly dependent on the energy metabolism of the cell. This fact fits very well into the
picture of "repair-replication", as very recent biochemical investigations
show that enzymes mediating the rejoining of open DNA-strands need
ATP or NAD as cofactors [40, 50]. The inhibition of recovery from sublethal damage by actinomycin D [12] of of LHR by DNA-complexing dyes
[42] also favours this hypothesis.
Conclusions
Obviously we are far from a real understanding of cellular recovery
processes. All the models discussed give no more than hypotheses for certain aspects. The interesting feature is the hope that we can obtain by these
studies not only radiobiological knowledge but also a deeper insight into
the normal functioning of the cell.