Effect of simultaneous administration of leupeptin on induction of bladder tumors in rats by N-butyl-N-(4-hydroxybutyl)-nitrosamine.

Male Wistar rats were given a diet containing 0.1% leupeptin, a microbial protease inhibitor, and drinking water containing 0.01% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 8 weeks. Leupeptin did not have any detectable effect on the induction of bladder tumors by BBN in week 40, in terms of the weight of the bladder including the tumor, the number of tumors per bladder, the extent of invasion, or the incidences of hyperplasia, papilloma, and cancer. This result is in marked contrast to the previous findings that leupeptin enhanced BBN-induced bladder carcinogenesis when administered continuously after BBN-treatment.