Iron homeostasis, oxidative stress, and DNA damage

Cellular DNA damage under prooxidant conditions has been shown to be mediated by iron. In fact, iron is an important element in the establishment of a prooxidant status in the cell. It is discussed that there exists a mutual dependence between iron metabolism and oxidative stress. Changes in the former by means of genetic manipulation bring about modification in the redox status as judge by oxidative damage in DNA. On the other hand, the induction of a cellular prooxidative condition activates the protein IRP (iron regulatory protein) in a way that renders the cell more able to take up iron. The possible implications of these results is discussed in the light of recent findings reported in the literature on hydrogen peroxide as a signaling species for cell proliferation. The question of DNA strand break formation under prooxidant conditions is reviewed from the viewpoint of which agent is more important: an oxidant generated by Fenton type reaction or Ca2+-activated nucleases. The presence of iron in the nucleus is reviewed. Results have been produced indicating that the larger concentration of this metal in the nucleus, as compared to the cytosol, seems to be explained by an iron-type P-ATPase. There is no explanation, presently, for iron presence in the nucleus, but it certainly imposes a prooxidant trend that needs to be counterbalanced in some way, and evidence is reviewed that nuclear metallothionein plays a role in this regard. (C) 1997 Elsevier Science Inc.