METABOLIC-FATE OF N-BUTYL-N-(4-HYDROXYBUTYL)NITROSAMINE HOMOLOGS IN THE RAT, IN RELATION TO THEIR ORGANOTROPIC CARCINOGENICITY TO THE URINARY-BLADDER

  • 1 January 1981
    • journal article
    • research article
    • Vol. 72  (1) , 113-122
Abstract
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 homologues 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)nitrosamnine, N-alkyl-N-(carboxymethyl)nitrosamine, N-alkyl-N-(2-oxopropyl)nitrosamine) and the glucuronic acid conjugate of N-alkyl-N-(4-hydroxybutyl)nitrosamine. A possible correlation of urinary excretion of the N-alkyl-N-(3-carboxypropyl)nitrosamine with selective induction of bladder cancer by the N-alkyl-N-(4-hydroxybutyl)nitrosamine in rats is discussed.

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