Effect of leupeptin, a protease inhibitor, on induction of bladder tumors in rats by n-butyl-n-(4-hydroxybutyl)nitrosamine.

Leupeptin, isolated from Actinomycetes, is a potent and specific inhibitor of proteases. We found that the administration of leupeptin enhanced that size of urinary bladder tumors induced in rats by the oral administration of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). BBN was given as a 0.05% solution in the drinking water for 6 weeks, and then animals were fed a diet with or without 0.1% leupeptin for 30 weeks. The average weight of the bladders with tumors in rats fed a leupeptin diet was about eight times that of rats on a diet without leupeptin, though the incidences and average numbers of tumors in the bladders were similar in the two groups.