THE FIELD BEAN PROTEASE INHIBITOR CAN EFFECTIVELY SUPPRESS 7,12-DIMETHYLBENZ[A]ANTHRACENE-INDUCED SKIN TUMORIGENESIS IN MICE

Prolonged topical treatment with protease inhibitors (PIs) both synthe tic and of bacterial origin have been shown to prevent carcinogen init iated and croton oil or phorbol acetate promoted skin carcinogenesis i n mice. However, no one has yet examined the possibility of a purified PI of plant origin to block skin carcinogenesis by sustained local tr eatment. We therefore studied this aspect using a purified PI from fie ld bean (FBPI) in Swiss albino mice. Groups of 8-week-old mice were ta ken and treated differently. Group I mice were treated with 100 mu l o f acetone alone, while mice of Group II were treated with a single hig h (150 mu g) dose of 7,12-dimethylbenz[a]anthracene in acetone and 2 w eeks later they were treated with a high concentration (125 mu g) of c roton oil thrice weekly. Mice of Groups III, IV and V were treated exa ctly as described for mice of Group II, but 4 h after croton oil treat ment they were further treated with an aqueous solution of 1 mg, 2 mg of FBPI or 2 mg of heal-inactivated FBPI, respectively. Treatment of a ll groups was continued until the mice were 25 weeks old, the appearan ce of tumors being recorded during the period. Our findings showed tha t treatment of carcinogen and croton oil exposed mice of Groups III an d IV with two different doses of FBPI not only brought about appreciab le delay in the appearance of tumors but also significant (P < 0.025-0 .001) suppression of tumor incidence at nearly all times of promotion. Additionally, it lowered significantly (P < 0.01-0.001) the tumor mul tiplicity and the tumor appearance rate compared to mice of Groups II and V. These effects of FBPI appeared to be dose related. Lack of resp onse with heat-inactivated FBPI indicated that these actions of FBPI w ere related to its PI activity. The study thus confirmed that topical treatment with a legume-derived PI can effectively suppress skin carci nogenesis.