Copper-nitrilotriacetate (Cu-NTA) is a potent inducer of proliferative response both in liver and kidney but is a complete renal carcinogen

Earlier we have shown that ferric-nitrilotriacetate (Fe-NTA) is a hepatic a s well as renal tumor promoter and acts by elaborating oxidative stress. In this study we show that copper-nitrilotriacetate (Cu-NTA) is a potent indu cer of proliferative response both in liver and kidney but is a complete re nal carcinogen. Similar to Fe-NTA, Cu-NTA has an ability to induce hepatic ornithine decarboxylase (ODC) activity dose-dependently. The maximum induct ion in hepatic ODC activity was observed 12 h after Cu-NTA treatment. Howev er, renal ODC activity showed no significant changes at any time point and dose regimen studied. Similarly, hepatic and renal DNA synthesis which are measured as [H-3]thymidine incorporation were increased dose-dependently in both the organs after Cu-NTA treatment. Unlike Fe-NTA, Cu-NTA administrati on had no significant effect on hepatic and renal glutathione, and on the a ctivities of glutathione reductase, glutathione-S-transferase and catalase. In liver, saline-alone, DEN-alone, Cu-NTA-alone or DEN + Cu-NTA treated an imals showed no hepatic tumors. Liver histology from only DEN-initiated and saline-treated control animals showed occasional appearance of a typical c ell with large nucleus. Treatment of Cu-NTA to uninitiated and initiated an imals showed more or less similar hepatic histology. Treatment of Cu-NTA to DEN-initiated animals resulted in the proliferative changes characterized by extensive hepatocellular hyperplasia. In case of kidney, the treatment o f Cu-NTA to both the DEN-initiated and uninitiated animals led to the devel opment of renal cell tumors. Treatment of Cu-NTA to the uninitiated animals produced renal cell tumors in about 18.7% animals. However, treatment of C u-NTA to the DEN-initiated animals led to the development of renal cell tum ors in 77.7% animals, of which most of the tumors were bilateral. However, DEN-initiated and saline-treated control animals showed no evidence of tumo rs. Our data indicate that Cu-NTA is a potent inducer of proliferative resp onse both in liver and kidney but is a complete renal carcinogen.