Kuntse E, Greve T, Veber Zh
Department of Pathology, University of Göttingen, Germany.
Arkh Patol. 1992;54(11):32-9.
In the present experiments the dependence of tumour induction upon the different phases of the cell cycle in the proliferating urinary bladder was examined. For stimulation of urothelial proliferation, a one-third resection of the bladder was performed in female Wistar rats. To synchronize the proliferating urothelial cells, hydroxyurea was given. The direct-acting urothelial carcinogen N-methyl-N-nitrosourea (MNU) was administered as a single intravesical dose during different cell cycle phases. The incidence of urothelial bladder tumors was 32.6% in the controls. By comparison, the tumour incidences were 18.9, 9.3, 21.7, 26.3, 25.0 and 30.0%, respectively, when MNU was instilled during the late Gi-, early and late S-, G2+M-, and early and late postmitotic phase. The results obtained from a total of 283 rats clearly document a cell cycle specific inhibition of tumour development in the proliferating urinary bladder particularly when the carcinogen was administered during the early S-phase. MNU has also been shown to produce mesenchymal tumours in the bladder (overall incidence: 4.9%) as well as urothelial tumours in the renal pelvis (3.2%) and ureters (1.4%).
在当前实验中，研究了膀胱肿瘤诱发与增殖性膀胱细胞周期不同阶段的相关性。为刺激尿路上皮增殖，对雌性Wistar大鼠进行膀胱三分之一切除术。为使增殖的尿路上皮细胞同步化，给予羟基脲。在不同细胞周期阶段，经膀胱单次给予直接作用的尿路上皮致癌物N-甲基-N-亚硝基脲（MNU）。对照组膀胱尿路上皮肿瘤发生率为32.6%。相比之下，当在G1晚期、S期早期和晚期、G2+M期以及有丝分裂后早期和晚期滴注MNU时，肿瘤发生率分别为18.9%、9.3%、21.7%、26.3%、25.0%和30.0%。从总共283只大鼠获得的结果清楚地证明，在增殖性膀胱中肿瘤发生存在细胞周期特异性抑制，特别是当致癌物在S期早期给予时。MNU还被证明可在膀胱中产生间充质肿瘤（总发生率：4.9%）以及肾盂（3.2%）和输尿管（1.4%）中的尿路上皮肿瘤。
