Induction of epithelial neoplasms in the urinary bladder of the dog by intra‐vesical injection of a chemical carcinogen

Bonser, Georgiana M.; Crabbe, J. G. S.; Jull, J. W.; Pyrah, L. N.

doi:10.1002/path.1700680228

Cited by 15 publications

(1 citation statement)

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“…In 1969, Deichmann & Radomski when referring to 2-naphthylamine remarked that "after 30 years of investigation the challenge still remains; what is the active carcinogen of these aromatic amines?" It had been recognized very early that 2-naphthylamine per se was not carcinogenic after implantation into the bladder of 8 mice (Bonser et al, 1952) and instillation of 2-naphthylamine into the bladder of one dog (Bonser et al, 1954). Boyland and his colleagues (Boyland et al, 1957) suggested the active urinary pre-carcinogen might be 2 -amino -1 -napthylglucuronide which, when hydrolysed in urine by P-glucuronidase, could release 3,2-amino-i -naphthol, which they postulated was the ultimate reactive carcinogen.…”

Section: Discussionmentioning

confidence: 99%

The induction of rat bladder cancer by 2-naphthylamine

Hicks¹,

Wright²,

Wakefield³

1982

Br J Cancer

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Summary.-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.

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Section: Discussionmentioning

confidence: 99%

The induction of rat bladder cancer by 2-naphthylamine

Hicks¹,

Wright²,

Wakefield³

1982

Br J Cancer

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DNA adduct formation in primary mouse embryo cells induced by7H-dibenzo[c,g]carbazole and its organ-specific carcinogenic derivatives

Gábelová

Périn‐Roussel

Jounaïdi

et al. 1997

Environ. Mol. Mutagen.

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The nuclease P1 modification of the 32P‐postlabeling technique was used to study the biological activity of 7H‐dibenzo[c,g]carbazole (DBC) and some of its derivatives, including N‐methyldibenzo[c,g]carbazole (N‐MeDBC), 5,9‐dimethyldibenzo[c,g]carbazole (5,9‐diMeDBC), 5,9, N‐trimethyldibenzo[c,g] carbazole (5, 9, N‐triMeDBC), 6‐methoxydibenzo[c, g]carbazole (6‐McODBC), N‐acetyldibenzo[c,g]carbazole (N‐AcDBC), N‐hydroxymethyldibenzo[c,g]carbazole (N‐HMeDBC) in primary mouse embryo cells. A very good correlation was found between carcinogenic specificity in vivo of these N‐heterocyclic aromatic hydrocarbons and their DNA‐adduction in vitro. Primary mouse embryo cells were able to metabolize and detect tissue‐specific sarcomagens N‐MeDBC and 6‐MeODBC as well as derivatives with both sarcomagenic and hepatocarcinogenic activity, DBC, N‐AcDBC, and N‐HMeDBC. The strong specific hepatocarcinogen 5,9‐diMeDBC in vivo, did not induce any DNA‐adducts in the embryo cells, which suggests that the enzymatic composition of the target tissue probobly is the determining factor in the organ specificity of this derivative. 5,9,N‐triMeDBC, derivative without any carcinogenic activity in vivo, did not induce any DNA‐adducts in primary mouse embryo cells. Pretreatment of cells with 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) apparently stimulated DNA‐adduct formation in the cells exposed to DBC, 6‐MeODBC, and N‐MeDBC. No or a very slight effect of TCDD on DNA‐adduct formation was found in cells exposed to N‐HMeDBC and N‐AcDBC. Preliminary results have shown that TCDD slightly induced cytochrome P4501A1 linked ethoxyresorufin O‐deethylase (EROD) activity in primary mouse embryo cells. These data suggest the role of cytochrome P4501A1 in the metabolism of DBC derivatives with sarcomagenic activity. Environ. Mal. Mutagen. 30:56–64, 1997 © 1997 Wiley‐Liss, Inc.

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