Protective Action of Adult T-Cell Leukemia-Derived Factor (ADF)/Thioredoxin (TRX) Against Oxidative Damage in the Kidney of Mice Treated with a Renal Carcinogen, Ferric Nitrilotriacetate: Induction and Nuclear Translocation of ADF/TRX

The water-soluble chelate complex of nitrilotriacetate (NTA) with fer­ ric ion is a potent renal carcinogen by parenteral administration. Re­ peated intraperitoneal injections of ferric nitrilotriacetate (Fe-NTA) to male rats and mice induce acute and subacute renal proximal tubular necrosis and a subsequent high incidence (60-92%) of renal cell carci­ noma (1,2). In this renal carcinogenesis model, involvement of reactive oxygen species (ROS) in the tissue damage is strongly suggested by a sharp increase in lipid peroxidation products [thiobarbituric acidreactive substances (TBARS), 4-hydroxy-2-nonenal (HNE), HNE-

modified proteins, malondialdehyde (MDA)-modified proteins] (2-5) and oxidative DNA damage such as 8-hydroxy-2'-deoxyguanosine (8OHdG) (6) or thymine-tyrosine cross-links (7).