The role of membrane damage in radiation-induced cell death.

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.