Short-term screening of promoters of bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated, unilaterally ureter-ligated rats.
The modifying effects of 17 environmental chemicals on the development of lesions in the urinary bladder of rats with unilateral ureteric ligation were investigated. Lesions were initiated by treatment of the animals with 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) for 2 weeks, and then test chemicals were given for 22 weeks. The lesions of the urinary bladder found were preneoplastic papillary or nodular hyperplasias (PN hyperplasias) and papillomas. Additions of sodium saccharin (5%), sodium o-phenylphenate (2%), butylated hydroxyanisole (2%), and sodium L-ascorbate (5%) to the diet had significant promoting effects on the incidences and numbers of PN hyperplasias and papillomas per 10 cm of basement membrane of the urinary bladder in this system. Sodium erythorbate (5%), ethoxyquin (0.8%) and carbazole (0.6%) significantly increased the incidence of PN hyperplasias. N-Nitrosopyrrolidine (0.02%) did not affect the incidence or number of PN hyperplasias but increased those of papillomas. Sodium o-phenylphenate also induced PN hyperplasias in rats without BBN-initiation. Ascorbic acid, ascorbic stearate, three dihydroxyphenols, methylhydroquinone, pyrogallol, quinoline, and uric acid did not show promoting activity in this test system. Thus, 8 of 17 chemicals tested had various promoting effects on urinary bladder carcinogenesis. These results show that this test system of BBN-initiated, unilaterally ureter-ligated rats should be useful for the detection of new bladder carcinogens and promoters.
D000818:Animals; D002085:Butylhydroxybutylnitrosamine; D002273:Carcinogens / Q000633:toxicity*; D008026:Ligation; D008297:Male; D010212:Papilloma / Q000139:chemically induced; D011230:Precancerous Conditions / Q000139:chemically induced; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D014513:Ureter / Q000502:physiology*; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
D002273:Carcinogens; D002085:Butylhydroxybutylnitrosamine