Iron chelators reduce chromosomal breaks in ataxia-telangiectasia cells

Role of H-Ferritin in Radiosensitivity of Human Glioma Cells

“…This is also presumably accompanied with impaired cell cycle arrest and enhanced DNA sensitivity. Our data are consistent with evidence that altering cellular iron status may influence ATM activity [44,45].…”

Iron loading and oxidative stress in theAtm−/−mouse liver

“…Our data support this identification of increased body iron in A-T and further enhance the importance of this by showing significant changes in clinically relevant iron indexes. In vitro iron chelation studies using A-T cell models have also shown significant improvements in cell viability as a direct result of iron chelation, demonstrating that intracellular iron is a contributing factor in the progression of cell damage in these models (35)(36)(37). A potential link has been identified between increased iron and neurons in A-T as Hmox1, an enzyme involved in OS defense that produces labile iron as a byproduct (14,39) and which has been shown to be significantly upregulated in the cerebellum of 3-mo-old Atm Ϫ/Ϫ mice (3).…”

“…Parallels between the phenotypic pathologies of these disorders and A-T are evident and suggest the possibility of similarities in some of the factors that contribute to disease progression. In spite of this, very few investigations have detailed iron studies in A-T disease (35)(36)(37). A study by Shackelford and coworkers (35) has reported nontransferrin bound iron, a highly reactive form of free iron, to be increased in A-T patients and Atm Ϫ/Ϫ mice.…”

“…In spite of this, very few investigations have detailed iron studies in A-T disease (35)(36)(37). A study by Shackelford and coworkers (35) has reported nontransferrin bound iron, a highly reactive form of free iron, to be increased in A-T patients and Atm Ϫ/Ϫ mice. Our data support this identification of increased body iron in A-T and further enhance the importance of this by showing significant changes in clinically relevant iron indexes.…”

“…Shackelford and coworkers (35)(36)(37) have previously shown that the sera of Atm Ϫ/Ϫ mice contain more labile iron than that of wild-type mice, and that iron chelation in colonyforming experiments increased the colony-forming and survival capacity of A-T cells. Given the significance of OS to A-T disease pathology, and the high capacity of iron to affect OS, it is surprising that the regulation of iron homeostasis within the Atm Ϫ/Ϫ mouse has not been reported previously.…”