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Trisodium nitrilotriacetate monohydrate: promoting effects on the development of renal tubular cell tumors in rats treated with N-ethyl-N-hydroxyethylnitrosamine.

The effect of trisodium nitrilotriacetate monohydrate [N,N-bis(carboxymethyl)glycine trisodium salt] (Na3NTA X H2O) on development of renal tubular cell tumors induced with N-ethyl-N-hydroxyethylnitrosamine [CAS:13147-25-6; 2-(ethylnitrosamino)-ethanol] (EHEN) was studied. Six-week-old male inbred W rats were given a diet containing 1,000 ppm of EHEN for 2 weeks and then a diet containing a high (10,000 ppm) or low (500 ppm) concentration of Na3NTA X H2O for 30 weeks. The rats were killed during week 32. The higher concentration of Na3NTA X H2O enhanced the development of renal tubular cell tumors and increased the number and size of tumors in rats treated with EHEN, but the lower concentration of Na3NTA X H2O did not. The incidence of renal tubular cell tumors in week 32 was 33% in rats treated with 1,000 ppm EHEN for 2 weeks, 100% in rats treated with 1,000 ppm EHEN for 2 weeks plus high Na3NTA X H2O diet for 30 weeks, and 39% in rats treated with 1,000 ppm EHEN for 2 weeks and then given low Na3NTA X H2O diet for 30 weeks. Numbers of atypical cell foci per kidney area (No./cm2) were 17.0 +/- 7.6 in rats treated with EHEN and high Na3NTA X H2O, 7.3 +/- 2.2 in rats treated with EHEN and low Na3NTA X H2O, 3.7 +/- 1.4 in rats treated with EHEN alone, and 1.0 +/- 2.4 in rats treated with high Na3NTA X H2O diet alone. Atypical cell foci retained a tubular pattern and consisted of basophilic cells with a large nucleus or clear cells with a small nucleus.