The effect of chelating agents on cellular iron metabolism.

1. The effect of iron chelators on iron uptake, ferritin and total protein synthesis was studied in cultured Chang cells. Desferrioxamine depressed ferritin synthesis and completely inhibited iron uptake by ferritin protein. Rhodotorulic acid reduced iron uptake by the cells but had little effect on ferritin synthesis. Diethylenetriamine pentaacetic acid produced complete inhibition of iron uptake and all protein synthesis. 2,3-Dihydroxybenzoic acid (2,3-DHB) had no effect in this system. 2. When 2,3-DHB was incubated with a liver homogenate, its subsequent addition to a Chang cell culture resulted in depression of ferritin synthesis, iron uptake into the protein and some depression of total protein synthesis. Pretreatment of rhodotorulic acid did not affect its properties. 3. Non-ferritin iron in the Chang cell cytosol was dialysable, available for binding to transferrin and formed chelates which appeared, on gel chromatography, to be of low molecular weight. Gel chromatography of cytosol after incubation of the cells with chelating agents showed non-ferritin iron to be in a similar form. 4. Loss of non-ferritin iron from the cells occurred only when the transferrin in the medium was unsaturated. In the presence of chelating agents non-ferritin iron was lost from the cells even when transferrin was 100% saturated. 5. The results confirm the presence of an intracellular labile iron pool which is available for chelation, and demonstration that different iron chelators have different metabolic effects.