Histochemistry of NADH diaphorase and gamma-glutamyltranspeptidase in rat bladder tumors

To improve identification of preneoplastic bladder cancer cells,we have studied two enzyme histochemical changes in bladdertumors induced in male Fisher 344 rats by the carcinogen N-butyl-N-(4-hydroxybutyl)-nitrosamine.In early areas of focal nodular hyperplasia there was a dramaticincrease in staining for NADH:menadione oxidoreductase (diaphorase)activity. In nonfocal areas as well, there were many individualcells with intense staining, while the controls were of uniformmoderate staining. Large papillomas and carcinomas often showedheterogeneous staining. - Glutamyltranspeptidase (GGT) was absentfrom normal urothelium and from all tumors except the most advancedcarcinomas and large papillomas. In old, carcinogen-exposedanimals, GGT activity was seen in the luminal surface of tumorsand in the interlesion urothelium. In newborn rats and in ratswith regenerative hyperplasia following wounding of the urothelium,the diaphorase staining was less than that in the untreatedadult. Our findings suggest that increased diaphorase activitymay serve to identify early islands of carcinogen-induced, enzymaticallyaltered bladder cells, while GGT will not.