Ferritin-iron increases killing of Chinese hamster ovary cells by X-irradiation

Stationary-phase Chinese hamster ovary cells were cultured in medium containing ferritin (approximately 19% iron by weight) added at concentrations ranging from 0 to 128 micrograms/ml. One set of cultures was unirradiated, and another set was exposed to 4.0 Gy of X-ray. Clonogenic cell survival was assessed in each set of cultures. In the absence of added ferritin, 4.0 Gy killed approximately 50% of the cells. In the absence of radiation, ferritin was not toxic at less than 48 micrograms/ml; above 48 micrograms/ml, toxicity increased with concentration. Apoferritin was not toxic at any concentration tested (up to 1000 micrograms/ml). Although 32 micrograms/ml ferritin, reflecting only a 3-6 fold increase in iron concentration over normal serum, was not toxic, it reduced the survival of X-irradiated cells by an additional 75%. These results indicate that a sublethal concentration of ferritin can be a potent radiosensitizer. This suggests the possibility that high body iron stores may increase susceptibility to radiation injury in humans.