Iron-induced oxidative damage in colon carcinoma (Caco-2) cells

Intestinal epithelial cells have an active apical iron uptake system that i s involved in the regulated absorption of iron. By the action of this syste m, intestinal cells acquire increasing amounts of iron with time. Since int racellular reactive iron is a source of free radicals and a possible cause of colon carcinoma, this study analyzed the oxidative damages generated by iron accumulation in Caco-2 cells. Cells cultured with increasing concentra tions of iron increased both total intracellular iron and the reactive iron pool, despite an active IRE/IRP system, which regulates intracellular iron levels. Increasing concentrations of iron resulted in increased protein ox idative damage, as shown by the immunoreactivity for 4-hydroxy-2-nonenal-mo dified proteins, and markedly induced DNA oxidation determined by 8-hydroxy -2'-deoxyguanidine production. Iron also impaired cell viability, resulting in increased cell death after 6 days of culture. In summary, iron accumula tion by intestinal Caco-2 cells correlated with oxidative damage to protein s and DNA. Oxidative damage finally resulted in loss of cell viability. The Fe-induced oxidative damage observed may be relevant in understanding the cascade of events associated with iron-mediated colon carcinogenesis.