The Effect of Ascorbic Acid Upon Bladder Uptake of β-Naphthylamine Metabolites 1

Abstract

The cause of bladder cancer is, in most instances, still a matter of speculation. More and more chemicals are added to the list of suspected carcinogens, in most instances on the basis of animal experiments. When cyclamate was found to be carcinogenic in mousebladder implantation studies (1), it was removed from the market. Since five naturally occurring tryptophan metabolites have been shown to be carcinogenic (2–8) by the same technique, it would follow logically that tryptophan should also be banned. This is obviously an absurdity, since tryptophan is an essential amino acid, and we must thus accept that carcinogenic substances are naturally occurring in the urine. Even though the concentration and types of carcinogens in the urine must be of obvious importance, results of work done in our laboratory have suggested that the redox potential of the urine is of equal, if not greater, importance (9). Several suspected carcinogens oxidize very readily (10), and we have previously shown that administration of ascorbic acid would prevent oxidation of 3-hydroxyanthranilic acid (11), as well as its carcinogenicity (8).

Since it is still controversial as to whether tryptophan metabolites can cause cancer of the uroepithelium in man, we felt it would be of interest to study the effect of ascorbic acid on the bladder reabsorption of Betanaphthylamine metabolites. β-naphthylamine is a proven potent bladder carcinogen in man (12), dogs (13), and nonhuman primates (14) when ingested orally, although uncertainty exists as to which and how many of the urinary metabolites are the potent carcinogens. We consequently in this study gave a single dose of tritium-labelled β-naphthylamine to a dog, and extracted the urinary metabolites. The effect of ascorbic acid upon the reabsorption of the metabolites by the rabbit bladders was then investigated.