Suppression of rat bladder carcinogenesis by alpha-difluoromethylornithine

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Oral administration of alpha-difluoromethylornithine (DFMO) at 0.5% or 0.2% in the drinking water had been demonstrated to suppress N-butyl-N-(4-hydroxybutyl)- nitrosamine-induced bladder caracinogenesis in rats. In the present study, lower doses of DFM (0.1%, 0.03%, 0.01%) were investigated for their possible inhibitory effects. Male Fischer rats of 35 each were given 0.05% BHBN containing water for 6 weeks and then 0.2%, 0.1%, 0.03%, 0.01% or 0% DFMO water for the following 34 weeks. At the end of treatment, the animals were killed and urinary bladders or other pertinent organs (submandibular gland, thyroid, parathyroid, trachea, lung, heart, liver, kidney, spleen, stomach, ileum, colon, prostate, seminal- vesicle, testis, skin, muscle, bone marrow) were examined histopathalogically. The incidences of bladder cancer in each DFMO dosis were 43% (0.2%), 40%(0.1%), 60%(0.03%), 57%(0.01%) and 77%(0%), respectively. The former two incidences were significantly suppressed. No histological changes attributable to DFMO were disclosed in other organs. These results indicated that bladder carcinogenesis induced by six week exposure to 0.05% BHBN is significantly inhibited by daily administration of DFM at the level of 0.1% or higher in drinking water.