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.
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.
D000818:Animals; D002273:Carcinogens / Q000652:urine*; D055598:Chemical Phenomena; D002621:Chemistry; D002855:Chromatography, Thin Layer; D004938:Esophageal Neoplasms / Q000139:chemically induced; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D009374:Neoplasms, Experimental / Q000139:chemically induced; D009602:Nitrosamines / Q000652:urine*; D051381:Rats; D011919:Rats, Inbred Strains; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D009602:Nitrosamines; C032849:N,N-diamylnitrosamine; C013161:N-nitroso(di-n-propyl)amine