Suppression of rat bladder carcinogenesis by alpha-difluoromethylornithine

已证明在饮用水中口服0.5%或0.2%的α-二氟甲基鸟氨酸（DFMO）可抑制N-丁基-N-（4-羟丁基）-亚硝胺诱导的大鼠膀胱癌生成。在本研究中，研究了较低剂量的DFM（0.1%，0.03%，0.01%）可能的抑制作用。雄性Fischer大鼠，每组35只，给予含0.05%BHBN的水6周，然后给予0.2%、0.1%、0.03%、0.01%或0%DFMO水34周。给药结束时，处死动物，并对膀胱或其他相关器官（下颌下腺、甲状腺、甲状旁腺、气管、肺、心脏、肝脏、肾脏、脾脏、胃、回肠、结肠、前列腺、精囊、睾丸、皮肤、肌肉、骨髓）进行组织病理学检查。膀胱癌的发生率分别为43%（0.2%）、40%（0.1%）、60%（0.03%）、57%（0.01%）和77%（0%）。前两种发生率明显受到抑制。在其他器官中未发现可归因于DFMO的组织学变化。这些结果表明，在饮用水中每天给予0.1%或更高水平的DFM，可显著抑制0.05%BHBN暴露6周诱发的膀胱癌发生。

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.