Shibata M A, Hasegawa R, Sano M, Shirai T, Fukushima S
First Department of Pathology, Nagoya City University Medical School.
Jpn J Cancer Res. 1991 Oct;82(10):1077-84. doi: 10.1111/j.1349-7006.1991.tb01760.x.
The post-initiation enhancing activities of the non-genotoxic agent NaHCO3 and the genotoxic agent N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) in combination with uracil-induced urolithiasis were investigated in a rat bladder carcinogenesis model. Animals were treated with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 4 weeks, and then 3% uracil was given for 3 weeks in the early (weeks 4-7), middle (weeks 8-11) or late (weeks 12-15) post-initiation phase. In addition, administration of 3% NaHCO3, 20 ppm EHBN or no chemical supplement was performed for the 13 weeks when the rats were not receiving BBN or uracil. NaHCO3 in sequential combination with early and middle stages uracil treatment strongly enhanced tumorigenesis in the urinary bladder, while EHBN treatment amplified lesion development at the middle stage only of uracil treatment. DNA synthesis and associated epithelial surface alterations observed by scanning electron microscopy tended to be increased in the NaHCO3 and EHBN groups without BBN initiation, independently of uracil treatment timing. The present results demonstrated that uracil-induced urolithiasis during the middle post-initiation phase is highly active in enhancing bladder tumor development under the influence of a promoter or carcinogen.
在大鼠膀胱癌发生模型中，研究了非遗传毒性剂碳酸氢钠（NaHCO3）和遗传毒性剂N-乙基-N-（4-羟丁基）亚硝胺（EHBN）联合尿嘧啶诱导的尿路结石形成后的启动后增强活性。动物先用0.05%的N-丁基-N-（4-羟丁基）亚硝胺（BBN）处理4周，然后在启动后的早期（第4 - 7周）、中期（第8 - 11周）或晚期（第12 - 15周）给予3%的尿嘧啶处理3周。此外，在大鼠未接受BBN或尿嘧啶的13周内，给予3%的NaHCO3、20 ppm的EHBN或不给予化学补充剂。NaHCO3与早期和中期尿嘧啶处理顺序联合，强烈增强了膀胱肿瘤的发生，而EHBN处理仅在尿嘧啶处理的中期放大了病变发展。在没有BBN启动的情况下，通过扫描电子显微镜观察到的DNA合成和相关上皮表面改变在NaHCO3和EHBN组中倾向于增加，与尿嘧啶处理时间无关。目前的结果表明，启动后中期尿嘧啶诱导的尿路结石形成在启动子或致癌物的影响下，在增强膀胱肿瘤发展方面具有高度活性。
