The induction of rat bladder cancer by 2-naphthylamine

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Abstract
The widely held belief that 2-naphthylamine is not carcinogenic for the rat has been re-examined. Twenty female Wistar rats were dosed by gastric intubation weekly for 57 weeks with 2-naphthylamine, 300 mg/kg body wt, in arachis oil and 20 controls were given arachis oil alone. Animals which became moribund were killed during the course of the experiment and the remainder after 100 weeks. A 2-naphthylamine-treated animal died at 21 weeks, all others survived 57 weeks or longer. The urinary tracts of all but two 2-naphthylamine-treated animals, which were found dead and cannibalized, were examined histologically. No neoplastic disease of the urinary tract was present in control animals. In 10 of the 2-naphthylamine-treated rats there was neither neoplasia nor hyperplasia of the urothelium, but 4 of the 18 examined histologically had large, macroscopically visible bladder cancers, one of these also had bilateral transitional cell tumours of the kidney calyces and multiple tumours in both ureters. Another animal had bilateral urothelial cancers in the ureters. The histology and ultrastructure of these urothelial cancers were comparable to those of rat transitional-cell carcinomas experimentally induced with other chemical carcinogens. These results, considered in the context both of early and more recently published biochemical studies of 2-naphthylamine metabolism in the rat, support the possibility that production of the active carcinogenic metabolite in this species may be influenced by a pH-dependent, non-enzymic mechanism in the urine, which could account for individual, strain- and diet-related variations in response in the rat.