Iron is essential for cellular growth, and various ferroproteins and
heme-containing
proteins are involved in a myriad of cellular functions, such as
DNA synthesis,
oxygen transport, and catalytic reactions. As a consequence,
iron deficiency causes pleiotropic effects, such as
hypochromic microcytic anemia and growth disturbance, while
iron overload is also deleterious by oxidative injury. To prevent the generation of
iron-mediated
reactive oxygen species (ROS),
ferritin is synthesized to store excess
iron in cells that are consistent with the clinical utility of the serum
ferritin concentration to monitor the
therapeutic effect of
iron-chelation. Among the animal models exploring
iron-induced oxidative stress,
ferric nitrilotriacetate (
Fe-NTA) was shown to initiate hepatic and renal lipid peroxidation and the development of
renal cell carcinoma (RCC) after repeated
intraperitoneal injections of
Fe-NTA. Here, current understanding of
Fe-NTA-induced oxidative stress mediated by
glutathione-cycle-dependent
iron reduction and the molecular mechanisms of renal
carcinogenesis are summarized in combination with a summary of the relationship between the pathogenesis of human RCC and
iron metabolism. In addition to
iron-mediated
carcinogenesis, the ferroptosis that is triggered by the
iron-dependent accumulation of lipid peroxidation and is implicated in the
carcinogenesis is discussed.