The metabolic fate of
N, N-dipropylnitrosamine (
DPN) and N, N-dipentyl-(=diamyl)
nitrosamine (DAN), which induced
tumors principally in the liver and esophagus but not in the urinary bladder, was studied in the rat, in order to elucidate the reason for this lack of carcinogenicity to the urinary bladder in contrast with the butyl homolog,
N, N-dibutylnitrosamine (DBN), a potent bladder
carcinogen. The principal urinary metabolite of
DPN was identified as the omega-oxidation product N-propyl-N-(2-carboxyethyl)
nitrosamine. The (omega-1)-oxidation product N-propyl-N-(2-hydroxypropyl)
nitrosamine and its
glucuronic acid conjugate were also characterized as metabolites. The principal urinary metabolite of DAN was N-amyl-N-(2-carboxyethyl)
nitrosamine, which was formed by metabolic shortening of the amyl chain by omega- and beta-oxidations according to the Knoop mechanism. Besides this, seven compounds oxidized at omega-, (omega-1)-, (omega-2)-, and (omega-3)- positions of one or both amyl chains were isolated and characterized, some of which were shown to be also present as the corresponding
glucuronide. The metabolic pattern of
DPN and DAN was compared with that of DBN, and the lack of carcinogenicity of the former N-
nitrosamines to the urinary bladder of rats is discussed on the basis of their urinary metabolites.