Conditions for inhibiting and enhancing effects of the protease inhibitor antipain on x-ray-induced neoplastic transformation in hamster and mouse cells.

Using cultured normal hamster embryo cells and the heterploid mouse C3H cell line 10T1/2, clone 8, we have studied the effect of the protease inhibitor antipain on x-ray-induced neoplastic transformation. We found in both cell systems that, while there was no effect on cell survival as compared to irradiated controls, the addition of antipain at a concentration of 6 microgram/ml to the cultures 24 hr prior to irradiation resulted in enhanced transformation as compared to the frequency in cultures exposed to radiation alone. Yet the addition of antipain to cultures 10 min after irradiation resulted in a decreased transformation rate. This decrease was not found when antipain was added to the mouse cells 24 hr after irradiation or to the hamster cells 48 hr after irradiation. These results suggest that the protease inhibitor antipain has more than one mechanism of action in modulating the fixation and expression of transformation by x-irradiation, possibly by the modification of DNA repair.