Comparison of the Bowman-Birk protease inhibitor to WR1065 for protection against radiation-induced DNA, cellulr and tissue damage

Background - Protease inhibitors and aminothiols have previously been shown to suppress radiation-induced cellular transformation and carcinogenesis. In this study the Bowman-Birk protease inhibitor and WR1065 were compared for protection against radiation-induced DNA, cellular and tissue damage. We have previously demonstrated a convincing chemopreventive effect with a diet containing 0.5% BBI for suppression of experimentally induced liver angiosarco mas and intestinal carcinomas. Previous studies by others have demonstrated the capacity of aminothiols to protect the intestinal mucosa from radiation injury. Methods - We used DNA strand scission, clonogenic survival of C3H/10T( 1/2 ) cells and, crypt colony survival to monitor the radioprotective capacity of BBI and WR1065. Results - WR1065 was found to be quite effective at reducing radiation-induced scission of plasmid DNA, whereas BBI had no effect on DNA strand scission (Fig. 1). In this investigation we found that doses of WR1065 that suppress radiation-induced malignant transformation of C3H/10T( 1/2 ) cells also yield obvious protection against radiation-induced cell killing (Fig. 2). Doses of BBI that have heen demonstrated to effectively suppress radiation-induced transformation of cells were without influence on survival of C3H10T( 1/2 )cells (Fig. 2). In this study, the ingestion of a diet containing 0.5% BBI showed no deleterious side effects on the number of cells per crypt or villi or the number of crypts per intestinal circumference (Table I). Furthermore, a diet containing BBI did not protect the intestine from radiation injury (Fig. 3). Discussion - These results suggest that anticarcinogenic protease inhibitors and aminothiols produce their chemoprotective effects by different mechanisms. Because BBI does not reduce radiation-induced DNA strand scission, cell killing, or tissue injury, it may be a promising agent in the chemoprevention of secondary malignancies induced by cancer therapy agents.