FERRIC NITRILOTRIACETATE (FE-NTA) IS A POTENT HEPATIC TUMOR PROMOTER AND ACTS THROUGH THE GENERATION OF OXIDATIVE STRESS

Fe-NTA is a known renal carcinogen. However, little is known about its carcinogenic potential in liver. In this study we for the first time show that Fe-NTA is a potent hepatic tumor promoter. Fe-NTA administra tion induced dose dependently the hepatic ornithine decarboxylase (ODC ) activity several folds as compared to its activity in the saline-tre ated rats. Similarly, hepatic DNA synthesis which is measured as [H-3] thymidine incorporation in DNA is also increased following Fe-NTA trea tment. The effects of Fe-NTA were similar to other tumor promoters not only with respect to inducing ODC activity and [H-3]thymidine incorpo ration in DNA but also in depleting antioxidant armory of the tissue. Fe-NTA depleted levels of glutathione to about 35% of the saline-treat ed control and activities of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase and glucose 6-phosphate dehydrogena se decreased significantly (45-55% of saline-treated control). Concomi tant with the depletion in antioxidant armory, Fe-NTA augmented hepati c microsomal lipid peroxidation more than three folds. The pretreatmen t of rats with antioxidants BHA or BHT diminished the observed effects of Fe-NTA. Our data indicate that Fe-NTA is a potent hepatic tumor pr omoter and acts through a mechanism involving oxidative stress. (C) 19 95 Academic Press.