Abstract
Iron is the most abundant transition metal in humans, and it plays a central role in metabolism. However, excess physiological iron may be toxic; it may increase the risk of cancer; and it has now been shown to increase cellular sensitivity to radiation injury. Increased available iron stores may enhance cell killing and genetic alterations through catalysis of free-radical reactions. This may lead to direct DNA damage or depletion of cellular reserves of reducing equivalents, thereby interfering with the maintenance of genomic integrity. Human epidemiological studies are being conducted to determine the effect of excess iron on cancer risk; experimental laboratory studies are probing the increased risk of radiation injury. In prospective studies of a sample of the U.S. population, high serum transferrin saturation was found to correlate directly with cancer risk over a 10-year period. In experimental studies using Chinese hamster ovary cells, ferritin (∼19% iron by weight) added to the growth medium resulted in iron concentrations of only about five times the physiological norm. These concentrations were found to increase (by an additional 75%) cell killing by 4 Gy of X rays. The same doses of ferritin without X rays were not toxic, and apoferritin (the iron-free protein) had no effect.