Chapter 6. Ferroptosis and Oxidative DNA Damage

Genomic DNA is a blueprint for the cell. No independent life on earth can live without iron. However, iron provides a double-edged sword; namely, anemia in deficiency and oxidative damage in excess through the Fenton reaction. Oxidative damage includes those in the genomic DNA, which may eventually lead to mutations. Indeed, excess iron has been associated with carcinogenesis. Evolutionally, after the era with an iron-rich ocean, the sulfur era started ∼2.5 billion years ago, which has been further overridden by the oxygen era ever since ∼1 billion years ago. Thus, the order of the major elements for electron transfer is Fe, S and O. Ferroptosis, a novel concept of regulated necrosis, can be interpreted as an imbalance between iron and sulfur, where the ratio of iron to sulfur is significantly increased. Acquisition of ferroptosis-resistance through mutations is recognized as a major pathogenesis of carcinogenesis. Oxygenomics approaches are used to examine loci in the genome vulnerable to oxidative damage. Many cancer-prone syndromes are associated with allelic inactivation of DNA repair enzymes. Conversely, there is a trial to use oxidative stress via non-thermal plasma to specifically kill cancer cells, based on the fact that cancer cells are more oxidatively stressed in comparison to non-tumorous cells.