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 necessaryfor the modification of radiation-induced transformation inC3H/10T1/2 cells by TPA and protease inhibitors. The resultsshow that: (i) the lowest effective dose of various proteaseinhibitors to suppress transformation in vitro varies over severalorders of magnitude; on a molar basis, the inhibitors of chymotrypsinappear to be the most effective protease inhibitors at suppressionof radiation-induced transformation in vitro, (ii) the proteaseinhibitors antipain and the Bowman-Birk (soybean) protease inhibitorhave no effect on radiation transformation when present onlyduring irradiation, (iii) the protease inhibitor antipain cansuppress radiation transformation in vitro when applied to proliferating‘initiated’ cells as late as 10 days and 13 celldivisions post-irradiation, and (iv) TPA treatment followinga 10-day protease inhibitor (antipain) exposure of X-irradiated‘initiated’ cells does not lead to promotion invitro. These results suggest that protease inhibitor treatmentof the initiated cells has irreversibly reverted cells to theiroriginal or ‘uninitiated’ condition which existedbefore irradiation.