METABOLIC-FATE OF N,N-DIPROPYLNITROSAMINE AND N,N-DIAMYLNITROSAMINE IN THE RAT, IN RELATION TO THEIR LACK OF CARCINOGENIC EFFECT ON THE URINARY-BLADDER

  • 1 January 1981
    • journal article
    • research article
    • Vol. 72  (4) , 552-561
Abstract
The metabolic fate of N,N-dipropylnitrosamine (DPN) and N,N-dipentyl(=diamyl)nitrosamine (DAN), which induce 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 (the butyl homolog, N,N-dibutylnitrosamine (DBN) is a potent bladder carcinogen). The principal urinary metabolite of DPN was 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 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, 7 compounds oxidized at .omega.-, (.omega.-1)-, (.omega.-2)-, and (.omega.-3)-positions of 1 or both amyl chains were isolated and characterized, some of which were 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.