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Effects of Protease Inhibitors on Radiation Transformation in Vitro¹

Laboratory of Radiobiology, Harvard University School of Public Health, Boston, Massachusetts 02115

We have investigated the effects of three protease inhibitors, antipain, leupeptin, and soybean trypsin inhibitor, on the induction of oncogenic transformation in mouse C3H10T cells by X-rays. The patterns of inhibition by the three protease inhibitors were different. Antipain was the most effective, having the ability to suppress completely radiation transformation as well as radiation transformation enhanced by the phorbol ester promoting agent 12-O-tetradecanoylphorbol-13-acetate. The fact that antipain could suppress transformation when present for only 1 day following irradiation suggests that an effect on a DNA repair process might be important in its action. Leupeptin was less effective than antipain in its inhibition of radiation transformation. Soybean trypsin inhibitor suppressed only the promotional effects of 12-O-tetradecanoylphorbol-13-acetate on transformation. Our results suggest that there may be more than one protease involved in carcinogenesis.

¹ This research was supported by NIH Grants CA-22704 and ES-00002.

² To whom requests for reprints should be addressed.

Received 1/29/80. Accepted 2/25/81.

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