Oxygen as radiosensitizer: methods of analysis.
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Biomedical subjects
Publications and source records attributed to T Alper.
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Exposure of the scrapie agent to u.v. light at various wavelengths has shown that light of 237 nm is 4 to 5 times as effective in inactivating it as 'germicidal' wavelengths (250 to 270 nm); whereas with systems that depend on RNA or DNA for function, inactivation is most effective by wavelengths in the germicidal range and there is a minimum of response in the wavelength region round 240 nm. The action spectrum for the scrapie agent is reminiscent of the absorption spectrum for purified bacterial endotoxin, identified as a lipopolysaccharide complex. Dilute aqueous suspensions of scrapie agent were exposed to ionizing radiations in the presence or absence of oxygen. In dilute suspensions of test systems depending on the integrity of nucleic acid or protein, oxygen is almost invariably protective, but it was extremely sensitizing for inactivation of the scrapie agent, to an extent approached only in the case of membranous systems like lysosomes. Results of these two methods argue against dependence of the scrapie agent on an intrinsic nucleic acid moiety for ability to replicate. They suggest that a lipid fraction is an important component and to that extent provide additional support for the 'membrane hypothesis'.
Radiation-induced cell death is probably mediated primarily through deposition of energy, in single events, in a few vital macromolecules, or targets, the integrity of which is indispensable for proliferation. The genome is customarily regarded as the main target, but several lines of evidence support the inference that there are important consequences of events in nuclear membranes in eukaryotes, and plasma membrane in bacteria. The identification of a target depends to some extent on parallelism between modifications of biological damage to putative targets and to the cell as a whole. An important modifying procedure is removal of oxygen from the irradiated system. The presence of oxygen almost always sensitizes cells, but when model systems with biological function are irradiated extra-cellularly a high degree of sensitization by oxygen has been observed only with those in which membrane function is important. This makes sense because the lipid content of membranes renders them readily peroxidizable. When the quality of the radiation is changed, its effectiveness changes in opposite directions for subcellular model targets and for cells. This could be accounted for if interactions between lesions in membranes and in attached DNA play a substantial role in cellular radiation effects.
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The responses of five transplantable rat tumour lines to neutron and X irradiation have been compared by a method in which radiation-induced delay in tumour growth is used as a measure of effect. All the tumours were sarcomas and were irradiated at the same size, after growth in the same site, and under standard conditions. This group of similar tumours exhibited a large range in values of RBE in a dose range within which fractions of hypoxic cells did not detectably influence the result of X irradiation. Of the five tumour lines used, there were two pairs the members of which had a common origin and were histologically similar; the greatest differences in RBE values were between members of the pairs. These results suggest that the therapeutic use of high LET radiation cannot be expected uniformly to achieve local control better than conventional treatment of tumours at a given site, or even of a given histological type. Research is needed into methods that will have predictive value for the relative success of neutron therapy.
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