Iron overload in Chang cell cultures: biochemical and morphological studies.

Cultures of Chang cells have been studied during growth in media supplemented with ferric nitriloacetate. Iron loading of the cells occurs rapidly and is related to the iron concentration in the medium. A 50-fold increase in cellular iron content was obtained in some cultures. Most of the intracellular iron is membrane-bound and is seen on electron microscopy to be concentrated in discrete bodies. There is a rapid rise in cellular ferritin content after exposure to iron. Most of this is found in the cytosol. Iron taken into the cells is found equally in the cytosol and associated with membranes for the first 4 days of culture. After this time there is a rapid rise of membrane-bound iron associated with the formation of siderosomes which contain iron-rich ferritin cores. These siderosomes later evolve to contain irregular, electron-dense accumulations of iron. Initial exposure of cells to high iron concentrations causes rapid death but similar exposure after ferritin synthesis and siderosome formation has been stimulated by low iron concentrations is well tolerated. Cultures have been maintained for up to 26 weeks with no morphological signs of toxicity, though there is some impairment of proliferation at high iron concentrations. It is suggested that siderosome formation is part of the mechanism that protects the cell against iron toxicity.