Mechanisms of suppression of neoplastic transformation in vitro by low doses of low LET radiation

The suppression of neoplastic transformation of human hybrid cells in vitro by low doses (<10 cGy) of low LET radiation is a reproducible finding. Various mechanisms have been proposed to account for this observation. In our laboratory we are investigating four possible mechanisms. These are: (1)The selective killing of a transformation-sensitive subpopulation, (2)The upregulation of DNA repair, (3) The upregulation of reduced glutathione, and (4) Alteration in cell to cell communication. The fact that this suppression has been observed over a wide range of doses (0.04 to 10.0 cGy) indicates that it is unlikely that any one of these mechanisms is solely responsible. Indeed, it is probable that multiple mechanisms are involved and that they assume different importance at different doses. Data collected to date indicate that at a dose of 5 cGy, selective killing of the transformation sensitive G2 population could account, at least in part, for the observed suppression at that dose. We also have evidence that inhibition of DNA repair has a more potent abrogating effect on the degree of suppression in cells treated with 5 cGy compared to 0.5 cGy, indicating DNA repair may be more important at higher rather than lower doses. On the other hand we do not see any effect of buthionine sulfoxime-induced suppression of GSH on the transformation frequencies at either 0.1 or 4 cGy and conclude that upregulation of GSH is unlikely to be involved as a suppressive mechanism. Experiments are underway to examine the effect of inhibition of cell to cell communication