Fujii M, Mori H, Kato K, Takahashi M
J Urol. 1982 Dec;128(6):1349-52. doi: 10.1016/s0022-5347(17)53505-3.
Cytomorphologic or histologic changes in the tumorigenic process of the urinary bladder epithelium and the corresponding cytochemical alteration of lactate dehydrogenase (LDH) isoenzymes were studied in rats given a bladder carcinogen, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN). All the rats given BBN as drinking water for about 8 weeks showed hyperplasia of the bladder epithelium and all the rats given BBN for about 16 weeks developed papillomas. Carcinomas were noticed in 81 per cent of the animals given the carcinogen for 20 weeks. Urinary cytology showed no malignant cells before the 12th week but detected exfoliated malignant cells in 14 per cent of the rats given the carcinogen for 16 weeks. Malignant cells were found in 57 and 95 per cent of animals sacrificed at the 20th and 24th week respectively. Alteration of LDH isoenzyme pattern of cell extracts from the bladder epithelium that is characterized by shift to LDH4 and LDH5 from the preponderance of LDH1 and LDH2 in normal epithelium preceded the morphologic change; it appeared as early as the 8th week. A reversion of M/H ratio of the isoenzyme pattern could be proved cytochemically by means of urea inhibition that inactivates the LDH M-subunit.
对给予膀胱致癌物N-丁基-N-(4-羟基丁基)亚硝胺（BBN）的大鼠，研究了膀胱上皮致癌过程中的细胞形态学或组织学变化以及乳酸脱氢酶（LDH）同工酶相应的细胞化学改变。所有以饮水形式给予BBN约8周的大鼠均出现膀胱上皮增生，所有给予BBN约16周的大鼠均发生乳头状瘤。给予致癌物20周的动物中，81%出现了癌。尿液细胞学检查显示，在第12周之前未发现恶性细胞，但在给予致癌物16周的大鼠中，14%检测到了脱落的恶性细胞。在第20周和第24周处死的动物中，分别有57%和95%发现了恶性细胞。膀胱上皮细胞提取物的LDH同工酶模式改变，其特征是从正常上皮中以LDH1和LDH2占优势转变为LDH4和LDH5占优势，这一改变先于形态学变化；最早在第8周就出现了。通过尿素抑制使LDH M亚基失活的方法，可以在细胞化学上证明同工酶模式的M/H比值发生了逆转。
