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

Abstract

Earlier we have shown that ferric-nitrilotriacetate (Fe-NTA) is a hepatic as well as renal tumor promoter and acts by elaborating oxidative stress. In this study we show that copper-nitrilotriacetate (Cu-NTA) is a potent inducer of proliferative response both in liver and kidney but is a complete renal carcinogen. Similar to Fe-NTA, Cu-NTA has an ability to induce hepatic ornithine decarboxylase (ODC) activity dose-dependently. The maximum induction in hepatic ODC activity was observed 12 h after Cu-NTA treatment. However, 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 [3H]thymidine incorporation were increased dose-dependently in both the organs after Cu-NTA treatment. Unlike Fe-NTA, Cu-NTA administration had no significant effect on hepatic and renal glutathione, and on the activities of glutathione reductase, glutathione-S-transferase and catalase. In liver, saline-alone, DEN-alone, Cu-NTA-alone or DEN + Cu-NTA treated animals showed no hepatic tumors. Liver histology from only DEN-initiated and saline-treated control animals showed occasional appearance of a typical cell with large nucleus. Treatment of Cu-NTA to uninitiated and initiated animals 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 of Cu-NTA to both the DEN-initiated and uninitiated animals led to the development of renal cell tumors. Treatment of Cu-NTA to the uninitiated animals produced renal cell tumors in about 18.7% animals. However, treatment of Cu-NTA to the DEN-initiated animals led to the development of renal cell tumors in 77.7% animals, of which most of the tumors were bilateral. However, DEN-initiated and saline-treated control animals showed no evidence of tumors. Our data indicate that Cu-NTA is a potent inducer of proliferative response both in liver and kidney but is a complete renal carcinogen.

• Authors: U Giri, M Iqbal, M Athar
• Journal: International journal of oncology (Int J Oncol) Vol. 14 Issue 4 Pg. 799-806 (Apr 1999) ISSN: 1019-6439 [Print] Greece
• PMID: 10087332 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Carcinogens
• Organometallic Compounds
• Diethylnitrosamine
• cupric nitrilotriacetate
• Nitrilotriacetic Acid

Topics

• Animals
• Carcinogens (pharmacology)
• Cell Division (drug effects)
• Diethylnitrosamine (pharmacology)
• Kidney Neoplasms (chemically induced, pathology)
• Liver Neoplasms (chemically induced, pathology)
• Male
• Mice
• Nitrilotriacetic Acid (analogs & derivatives, pharmacology)
• Organometallic Compounds (pharmacology)