Airoldi L, Bonfanti M, Magagnotti C, Fanelli R
Cancer Res. 1987 Jul 15;47(14):3697-700.
The isolated rat urinary bladder was used to study this organ's capacity to metabolize chemical carcinogens. In our experimental conditions, the urinary bladder carcinogen N-nitrosobutyl(4-hydroxybutyl)amine was oxidized to N-nitrosobutyl(3-carboxypropyl)amine. A time-dependent increase was observed in the amount of N-nitrosobutyl(3-carboxypropyl)amine formed and simultaneous disappearance of N-nitrosobutyl(4-hydroxybutyl)amine added, indicating that the bladder can metabolize N-nitrosobutyl(4-hydroxybutyl)amine to the metabolite considered responsible for tumor induction in the urinary bladder of laboratory animals. At 15, 30, 60, and 120 min the percentages of N-nitrosobutyl(3-carboxypropyl)amine formed were 11, 22, 36, and 64%, respectively, and 62, 48, 37, and 26% of N-nitrosobutyl(4-hydroxybutyl)amine remained unchanged. When N-nitrosodibutylamine was introduced into the isolated urinary bladder and incubated for 120 min, its oxidized metabolites N-nitrosobutyl(4-hydroxybutyl)amine and N-nitrosobutyl(3-carboxypropyl)amine were formed, amounting to, respectively, 0.13 and 0.06% of the substrate added. The glucuronide of N-nitrosobutyl(4-hydroxybutyl)amine was incubated in the isolated rat urinary bladder both as a buffer and as a urine solution in order to detect cellular and urinary beta-glucuronidase activity. In both systems N-nitrosobutyl(4-hydroxybutyl)amine released was about 1% at 4 h and this percentage did not increase at 6 h. N-Nitrosobutyl(3-carboxypropyl)amine was detectable at 2 h and reached 0.2% of the substrate incubated at 6 h. The results indicate that the urinary bladder may play a role in activating bladder carcinogens.
采用离体大鼠膀胱来研究该器官代谢化学致癌物的能力。在我们的实验条件下，膀胱致癌物N - 亚硝基丁基（4 - 羟丁基）胺被氧化为N - 亚硝基丁基（3 - 羧丙基）胺。观察到形成的N - 亚硝基丁基（3 - 羧丙基）胺的量随时间增加，同时添加的N - 亚硝基丁基（4 - 羟丁基）胺同步消失，这表明膀胱能够将N - 亚硝基丁基（4 - 羟丁基）胺代谢为被认为是实验动物膀胱肿瘤诱导原因的代谢产物。在15、30、60和120分钟时，形成的N - 亚硝基丁基（3 - 羧丙基）胺的百分比分别为11%、22%、36%和64%，未发生变化的N - 亚硝基丁基（4 - 羟丁基）胺的百分比分别为62%、48%、37%和26%。当将N - 亚硝基二丁胺引入离体膀胱并孵育120分钟时，形成了其氧化代谢产物N - 亚硝基丁基（4 - 羟丁基）胺和N - 亚硝基丁基（3 - 羧丙基）胺，分别占所添加底物的0.13%和0.06%。将N - 亚硝基丁基（4 - 羟丁基）胺的葡糖醛酸化物作为缓冲液和尿液溶液在离体大鼠膀胱中孵育，以检测细胞和尿液中的β - 葡糖醛酸酶活性。在两个系统中，4小时时释放的N - 亚硝基丁基（4 - 羟丁基）胺约为1%，6小时时该百分比未增加。2小时时可检测到N - 亚硝基丁基（3 - 羧丙基）胺，6小时时达到所孵育底物的0.2%。结果表明膀胱可能在激活膀胱致癌物方面发挥作用。
