The conditions for the modification of radiation transformation in vitro by a tumor promoter and protease inhibitors

These experiments were designed to define the conditions necessary for the modification of radiation-induced transformation in C3H/10T1/2 cells by TPA and protease inhibitors. The results show that: (i) the lowest effective dose of various protease inhibitors to suppress transformation in vitro varies over several orders of magnitude; on a molar basis, the inhibitors of chymotrypsin appear to be the most effective protease inhibitors at suppression of radiation-induced transformation in vitro, (ii) the protease inhibitors antipain and the Bowman-Birk (soybean) protease inhibitor has no effect on radiation transformation when present only during irradiation, (iii) the protease inhibitor antipain can suppress radiation transformation in vitro when applied to proliferating 'initiated' cells as late as 10 days and 13 cell divisions post-irradiation, and (iv) TPA treatment following a 10-day protease inhibitor (antipain) exposure of X-irradiated 'initiated' cells does not lead to promotion in vitro. These results suggest that protease inhibitor treatment of the initiated cells has irreversibly reverted cells to their original or 'uninitiated' condition which existed before irradiation. (author)