Cytochemical studies of LDH isoenzymes in experimental bladder tumors

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.