Suppression of rat bladder carcinogenesis by alpha-difluoromethylornithine

饮水中加入0.5%或0.2%的α-二氟甲基鸟氨酸(DFMO)可抑制N-丁基-N-(4-羟基丁基)-亚硝胺诱导的大鼠膀胱癌的发生。在本研究中，研究了较低剂量(0.1%、0.03%、0.01%)DFM可能的抑制作用。雄性Fischer大鼠35只，灌胃0.05%牛血清白蛋白水6周，然后分别灌胃0.2%、0.1%、0.03%、0.01%或0%DFMO水34周。治疗结束后处死动物，取膀胱或其他相关器官(颌下腺、甲状腺、甲状旁腺、气管、肺、心脏、肝、肾、脾、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。膀胱癌发生率分别为43%(0.2%)、40%(0.1%)、60%(0.03%)、57%(0.01%)和77%(0%)。前两次事件都得到了明显抑制。在其他器官中没有发现可归因于DFMO的组织学变化。这些结果表明，饮水中加入0.1%或更高水平的DFM可显著抑制0.05%BHBN暴露6周所致膀胱癌的发生。

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.