Abstract
In an experiment primarily designed to evaluate the long-term dose dependence of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) administration, attention was concentrated on its influence on the renal pelvis. BBN was given at dosage levels of 50, 10, 5, 1, and 0 ppm in the drinking water to male F344 rats for 112 weeks. Even this life-span exposure did not cause any proliferative or neoplastic lesions of the renal pelvis/papilla despite papilloma and carcinoma induction by concentrations of 5 ppm and above in the urinary bladder. In a separate experiment, treatment with BBN or N-ethyl-N-(4-hydroxybutyl)nitrosamine (EHBN) at the dose of 500 ppm in the drinking water for 4 weeks was also found not to increase DNA synthesis in the renal pelvis/papilla epithelia. The fact that the bladder carcinogen BBN did not induce tumor development or an increment of DNA synthesis in the renal pelvis/papilla, which is lined like the bladder by transitional epithelium, strongly indicates that its target organ specificity is due to long urine stasis leading to prolonged metabolite (ultimate carcinogen) exposure only in the urinary bladder.
