Cellular proliferation and susceptibility to iron toxicity in iron loaded cell cultures.

Chang cells from human liver, grown in a medium supplemented with 161 mumol/l ferric nitrilotriacetate become iron loaded with an increase in their ferritin content and total iron content. Their viability is not impaired and they survive indefinitely in this state when subcultured at regular intervals. When the cells are grown in a confluent culture their mitotic index is reduced from 12% to less than 1%. In this state they survive normally in unsupplemented medium but when iron is added at 161 mumol/l concentration the cells die within 6 weeks. The toxic lesion appears to be induced within three weeks and is irreversible unless the cells are transferred to an iron-poor medium. Cultural conditions, particularly proliferative rate, appear to be important in determining susceptibility of the cells to iron toxicity. Cell age, hypopoxia and lysosomal enzyme have been assessed as factors that may affect susceptibility.