Metabolic fate of N-butyl-N-(4-hydroxybutyl)nitrosamine homologs in the rat, in relation to their organotropic carcinogenicity to the urinary bladder.

The metabolic fate of alkyl homologs (alkyl=methyl, ethyl, propyl, pentyl, and tert-butyl) of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN), a potent bladder carcinogen, was investigated in the rat, in order to elucidate any possible correlation of structure and metabolism with organospecific carcinogenicity to the urinary bladder of these N-nitrosamines. They were extensively metabolized in the rat, no unchanged compounds being found in the urine. The metabolic pattern of these alkyl homologs of BBN was essentially similar to that of BBN. Their principal urinary metabolite was the corresponding N-alkyl-N-(3-carboxypropyl)nitrosamine except in the case of the pentyl homolog. Minor metabolites characterized were subsequent transformation products of the principal metabolite by beta-oxidation according to the Knoop mechanism (i.e., N-alkyl-N-(2-hydroxy-3-carboxypropyl)nitrosamine, N-alkyl-N-(carboxymethyl)nitrosamine and N-alkyl-N-(2-oxopropyl)nitrosamine) and the glucuronic acid conjugate excretion of the N-alkyl-N-(c-carboxypropyl)nitrosamine with selective induction of bladder cancer by the N-alkyl-N-(4-hydroxybutyl)nitrosamine in rats is discussed.