de Camargo J L, Shirai T, Kato T, Asamoto M, Fukushima S
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1991 Nov;82(11):1220-5. doi: 10.1111/j.1349-7006.1991.tb01784.x.
Five non-genotoxic chemicals previously demonstrated to be bladder cancer promoters in 36-week in vivo assays for carcinogenesis were reevaluated in a 20-week experiment in order to assess the summation influence of dietary uracil, a component of RNA, on the development of (pre)neoplastic lesions. The test chemicals, sodium bicarbonate, sodium L-ascorbate, sodium citrate, butylated hydroxytoluene and ethoxyquin, were mixed into the diet at concentrations of 3%, 5%, 5%, 1% and 0.8%, respectively, and administered to male F344 rats after initiation with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in their drinking water for 4 weeks. The test chemicals were given from the 4th to the 8th and the 11th to 20th experimental weeks, uracil being administered at the level of 3% in the diet during the intervening period. Rats in the control group received only BBN and uracil. All animals were killed at week 20 and the bladders were evaluated for the occurrence of putative preneoplastic papillary or nodular (PN) hyperplasia and tumors. Significant increase in the occurrence of PN hyperplasia was observed in all groups initiated with BBN and fed uracil and test chemicals. Quantitative values for papillomas were also significantly increased except in the ethoxyquin-treated group. The results confirm that uracil given in the middle of the post-initiation stage enhances the promoting activity of chemicals and suggest that the use of this chemical might be useful to reduce the duration of current bioassays for bladder chemical carcinogens.
五种先前在为期36周的体内致癌试验中被证明为膀胱癌促进剂的非基因毒性化学物质，在一项为期20周的实验中重新进行了评估，以评估RNA成分尿嘧啶对（癌）前病变发展的综合影响。受试化学物质，碳酸氢钠、L-抗坏血酸钠、柠檬酸钠、丁基羟基甲苯和乙氧喹，分别以3%、5%、5%、1%和0.8%的浓度混入饲料中，并在雄性F344大鼠饮用含0.05% N-丁基-N-(4-羟基丁基)亚硝胺（BBN）的水4周启动致癌过程后给予。受试化学物质在实验第4至8周以及第11至20周给予，在此期间尿嘧啶以3%的水平添加到饲料中。对照组大鼠仅接受BBN和尿嘧啶。所有动物在第20周处死，并对膀胱进行评估，以确定是否存在假定的癌前乳头状或结节状（PN）增生及肿瘤。在所有用BBN启动并喂食尿嘧啶和受试化学物质的组中，均观察到PN增生发生率显著增加。除乙氧喹处理组外，乳头状瘤的定量值也显著增加。结果证实，在启动后阶段中期给予尿嘧啶可增强化学物质的促进活性，并表明使用这种化学物质可能有助于缩短当前膀胱化学致癌物生物测定的持续时间。
