THE RADIOSENSITIVITY OF RECURRENT CLONES OF AN IRRADIATED MURINE SQUAMOUS-CELL CARCINOMA IN THE IN-VITRO MEGACOLONY SYSTEM

Purpose: To measure changes in spontaneous growth rate and radiation r esponse in the progeny of irradiated squamous cell carcinoma cells. Ma terials and methods: Murine SCC cells of the line AT478 were grown as epithelial megacolonies in vitro, using both the original line and two subsequent passages derived from a clone that had recurred after a hi gh radiation dose, Radiosensitivity was evaluated in terms of local co ntrol following single dose irradiation of standard size megacolonies (0.8 cm(2)). In addition, original megacolonies were given a priming d ose of 20 Gy and the recurrent clones arising in situ were retreated a t three dose levels for analysis of curability. Results: A marked incr ease in radiosensitivity was observed in the megacolonies grown from i rradiated progeny as compared to original megacolonies, reflected in a shift of the TCD50 from 24.5 to 16.5 Gy. Direct parameter estimation from the cure data suggested that the underlying change was a lowered number of clonogenic 'stem' cells rather than increased cellular sensi tivity. A similar decrease in clonogen density was also apparent for t he recurrent clones in situ. The change in megacolony curability was p aralleled by a substantial growth retardation. Conclusion: The data de monstrate persistent changes in the progeny of irradiated SCC tumour c ells that affect both growth and radiosensitivity and are compatible w ith the expression of delayed reproductive death. (C) 1998 Elsevier Sc ience Ireland Ltd.