Trisodium Nitrilotriacetate Monohydrate: Promoting Effects on the Development of Renal Tubular Cell Tumors in Rats Treated With N-Ethyl-N-hydroxyethylnitrosamine2

Abstract
The effect of trisodium nitrilotriacetate monohydrate [N,N-bis(carboxymethyl)glycine trisodium salt] (Na3NTA·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·H2O for 30 weeks. The rats were killed during week 32. The higher concentration of Na3NTA·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·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·H2O diet for 30 weeks, and 39% in rats treated with 1,000 ppm EHEN for 2 weeks and then given low Na3NTA·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·H2O, 7.3±2.2 in rats treated with EHEN and low Na3NTAH2O, 3.7±1.4 in rats treated with EHEN alone, and 1.0±2.4 in rats treated with high Na3NTA·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.