Chemoprevention of exprimental bladder cancer

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Abstract
The chemopreventive efficacy of several compounds was evaluated in the N‐butyl‐N‐(4‐hydroxybuty) introsamine (OH)‐BBN)‐induced urinary bladder cancer model using C57BL/6xDBA/2F1 (BDF) male mice. Compounds were administered in a defined semipurified diet (AIN‐76‐A) either as single agents orin combination. As single agents and at the doses emplyed, 2‐α‐difluoromethylornithine (DFMO), piroxicam, oltpraz, and sodium moybdate effectively inhibited the incidence of trasitional cell carcinoma (TCC). 4‐Hydroxyphenyl retinamide (4‐HPR) was ineffective. Body weight gain and survival was not affected by thedoses of agents used. Combinations of two agents which increased efficacy were 4‐HPR+DFMO, DFMO+piroxicam, 4‐HPR+oltipraz, and DFMO+oltiprz. Three‐agent combinations which showed enhanced efficacy against TCC induction were 4‐HPR+Namolybdate+DFMO, 4‐HPR+DFMO+piroxicam, and 4‐HPR+DFMO+oltipraz. Although the three‐agent combinations were, for the most part, no more effective than the two‐agent combinations at the doses employed, all combination regmens signicantly reduced bladder incidence even when single agent administration did not.