Suppression of 3-methylcholanthrene-induced cellular transformation by timed administration of the Bowman-Birk protease inhibitor.

The Bowman-Birk protease inhibitor (BBI) is a legume-derived inhibitor of chymotrypsin and trypsin that has been shown to suppress cellular transformation and tumorigenesis. In the present investigation the effects of various BBI administration schedules were evaluated for suppression of 3-methylcholanthrene (3-MCA)-induced transformation of C3H/10T1/2 cells. At a concentration of 30 micrograms/ml, BBI demonstrated no toxicity to C3H/10T1/2 cells treated with 3-MCA. However, transformation of C3H/10T1/2 cells was significantly reduced when BBI was added to the cultures for a period of 14 or 42 days, starting immediately after exposure to the carcinogen. When BBI was administered only during the time of carcinogen exposure or alternatively beginning on day 15 and then continuously throughout the remainder of the 6-week transformation assay, it was ineffective for suppressing 3-MCA-induced cellular transformation. These findings indicate that BBI exerts its chemopreventive effect during the early stage of chemical carcinogen-induced cellular transformation.