The cell as single-hit detector

Abstract

The common manifestation of shoulders to survival curves, particularly for mammalian cells, has diverted attention from the importance of single-hit action as a radiobiological mechanism. Exponential survival is diagnostic for that mode of action. Of various interpretations of shouldered curves, the one best fitted by experimental facts is that single energy deposits can indeed be lethal; but many cells have capacity for a specific type of repair that is depleted, in a dose-dependent manner, until it ceases to function. The curve then assumes its exponential 'tail'. Genomic DNA seems an obvious target for the scoring of lethal hits. But a body of evidence indicates the presence in the cell of a second, chemically different, target, one in which oxygen interacts at the sites of energy deposits to fix damage, so causing radiosensitization. The nuclear membrane is a likely candidate. In cells proficient at repairing DNA, and irradiated with oxygen present, only a minority of lethal events are attributable to energy deposited in DNA. The hypothesis that hits are scored by .OH, based to a large extent on the phenomenon of chemical protection, is not justified by all the facts and is in conflict with some experimental observations. On the other hand, e-aq may well be damaging to DNA unless oxygen is present to act as scavenger.