INHIBITION OF BENZOPYRENE-INDUCED FORESTOMACH TUMORS BY FIELD BEAN PROTEASE INHIBITOR(S)

Protease inhibitors (PIs), particularly the soybean-derived Bowman-Bir k inhibitor, have proved to be powerful blockers of carcinogenesis in many in vitro and animal model systems, However, so far an ability of PIs to suppress gastric carcinogenesis has not been demonstrated, beca use of the anticipated 'hostile' acidic gastric environment for the PI to exert its action. We therefore examined the ability of a purified PI from the Indian legume the field bean (FBPI), when administered by gavage, to subdue benzopyrene (BP)-induced neoplasia of the forestomac h of mice, Forestomach tumors were produced in female Swiss albino mic e by oral administration of BP at a dose of 1 mg twice weekly for 4 we eks, Groups of mice were treated per os with an aqueous solution of FB PI for 3 months or more at a dose of 20 mg/kg once daily, six times a week, either from the initiation of carcinogenesis or after completion of the carcinogen treatment, Another group was treated likewise with autoclaved inactive FBPI, Mice of both the FBPI-treated groups showed statistically significant (P < 0.001) reductions in the multiplicity o f gastric tumors, with the tumor incidence being unaffected. However, the suppression of tumor multiplicity was appreciably (P < 0.01) more in the group that received FBPI treatment concomitantly with the carci nogen, The mice that were treated with heat-inactivated FBPI showed si milar tumor multiplicity to the BP-treated group, indicating that the oncopreventive activity of FBPI is related to its protease inhibitory capacity, These observations point to the potential of PIs as effectiv e chemoprotectors against gastric cancer in animals and, possibly, in humans as well.