The Relevance of Intra-Cellular Damage to Effects in the Complex Organism

Abstract

As the three previous papers in this Symposium have shown (Ord and Stocken 1968; Evans 1968; Court-Brown 1968) the exploration of radiation effects within the cell has its own intrinsic fascination quite apart from its relevance to an understanding of the phenomena which may be observed after irradiation of the complex organism, vertebrate or invertebrate. Whitmore (cf. Whitmore Gulyas and Botond 1965) has been one of the pioneer workers on a previously unsuspected phenomenon, the quantitatively substantial recovery of the ability to divide which occurs within the first hour or two after exposure to low LET radiation. In cultures of mammalian cells in vitro this kind of recovery was shown to have nothing to do with cell division, to occur at all stages of the cell cycle, and to be little, if at all, affected by a reduction in temperature which would be expected a priori to modify profoundly the rate of chemical reactions. Whitmore's technique for synchronising asynchronously dividing cell cultures by the selective suicide of DNA synthesising cells following the incorporation of radioactively labelled DNA precursors with high specific activity has a wide application (Whitmore and Gulyas 1966). Workers from his laboratory have proposed an interesting approach to the real meaning of “ability to divide” and “recovery” based on the idea that there is a certain probability of failure at each cell division and that this probability may be permanently increased by exposure to radiation (Till, McCulloch and Siminovitch 1964). Thus radiation damage may be expressed by failure of cell division not only at the first or second divisions after exposure but also at any subsequent division in the distant future.