Dose-dependent promoting effect of trisodium nitrilotriacetate monohydrate on urinary bladder carcinogenesis in Wistar rats pretreated with N-butyl-N-(4-hydroxybutyl)nitrosamine.

The dose-dependent effect of trisodium nitrilotriacetate monohydrate (Na3.NTA.H2O) as a promoter in 2-stage carcinogenesis in the urinary bladder of male Wistar rats was investigated. Carcinogenesis was initiated by administration of 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in the drinking water for 4 weeks, then Na3.NTA.H2O was given at 1%, 0.5% and 0.3% in the diet for 28 weeks, and rats were killed in week 32. The incidences and numbers of preneoplastic lesions [papillary or nodular hyperplasia (PN hyperplasia)] in rats treated with 0.3% to 1% Na3.NTA.H2O increased progressively with increasing concentration of Na3.NTA.H2O. The incidences of papillomas in rats treated with 1% and 0.5% Na3.NTA.H20 in the diet and the incidence of transitional cell carcinoma (TCC) of the urinary bladder in the rats treated with 1% Na3.NTA.H2O (P less than 0.05) were significantly higher than those in rats treated with BBN only. Administration of various doses of Na3.NTA.H2O without BBN did not cause any histological changes (PN hyperplasia, papilloma or TCC) in the urinary bladder. These findings showed that Na3.NTA.H2O is a potent promoter of urinary bladder carcinogenesis initiated by BBN in rats, and that its effect is dose-dependent.