Urothelial hyperplasia and neoplasia. III. Detection of nitrosamine production with different bacterial genera in chronic urinary tract infections of rats

Various agents have been implicated in inducing urothelial cancer. Although drugs, occupational and environmental carcinogens are more widely accepted as playing a major role as urothelial carcinogens, several investigations suggest that bacteria may play a role. The mechanism of how bacteria may interact with the host to augment the development of urothelial carcinoma is not well understood. Clinically, investigators have linked the development of infection, urinary stones and indwelling catheters with urothelial cancer. Other investigators have suggested that the mechanism may be related to the production of carcinogenic compounds (nitrosamines) which can be detected during urinary tract infection. In our laboratory, we showed that rats with chronic urinary tract infections produced increasing urinary levels of N,N dimethylnitrosamine over a 24 week period and that the production correlated with hyperplasia and early neoplasia of the bladder epithelium. Three bacterial genera were used and two of these (Escherichia coli and a protein sp.) showed production of increasing levels of urinary nitrosamine and correlated with infection. The purpose of this current study is to determine if other bacterial genera and strains can also produce similar increasing nitrosamine levels in the rat model of chronic urinary tract infection and thus provide evidence that a number of bacterial genera and strains can produce nitrosamines in vivo. Also, the histology of the chronically infected bladder was examined for hyperplasia and neoplasia.