IRON OVERLOAD IN CHANG CELL-CULTURES - BIOCHEMICAL AND MORPHOLOGICAL-STUDIES

Abstract

Chang [human liver] cell cultures were studied during growth in media supplemented with ferric nitriloacetate. Fe loading of the cells occurs rapidly and is related to the Fe concentration in the medium. A 50-fold increase in cellular Fe content was obtained in some cultures. Most of the intracellular Fe is membrane-bound and, based on EM, concentrated in discrete bodies. There is a rapid rise in cellular ferritin content after exposure to Fe. Most of this is found in the cytosol. Fe taken into the cells is found equally in the cytosol and associated with membranes for the 1st 4 days of culture. After this time there is a rapid rise of membrane-bound Fe associated with the formation of siderosomes which contain Fe-rich ferritin cores. These siderosomes later evolve to contain irregular, electron-dense accumulations of Fe. Initial exposure of cells to high Fe concentrations causes rapid death but similar exposure after ferritin synthesis and siderosome formation were stimulated by low Fe concentrations is well tolerated. Cultures are maintained for up to 26 wk with no morphological signs of toxicity, though there is some impairment of proliferation at high Fe concentrations. Siderosome formation apparently is part of the mechanism that protects the cell against Fe toxicity.