Iron Ion Induces Mitochondrial DNA Damage in HTC Rat Hepatoma Cell Culture-Role of Antioxidants in Mitochondrial DNA Protection from Oxidative Stresses

Direct observation of iron-induced conformational changes of mitochondrial DNA by high-resolution field-emission in-lens scanning electron microscopy.

“…This, in turn, can interact with Fe(II) to produce -OH radicals. They can damage DNA in many ways, particularly by inducing single-strand breaks (SSB) (8), which leads to changes in mtDNA conformation (9)(10)(11)(12)(13).…”

Iron(II) induces changes in the conformation of mammalian mitochondrial DNA resulting in a reduction of its transcriptional rate

“…Superoxide anion radicals (SAR) are produced in living mitochondria during the electron transfer of complexes I and III of the respiratory chain. SAR can, in turn, reduce iron(III) to iron(II) and maintain the Fenton reaction yielding OH radical which could nick the DNA strands producing breaks and unwinding of the mtDNA [3,4,18,21–23]. With the present experimental model, we previously demonstrated that mitochondria maintain electron transfer and coupling activity, so hydrogen peroxide is formed and the exogenous addition of iron(II) amplifies the Fenton reaction [10,14].…”

“…Incubation of mitochondria with iron(II) results in a dramatic change in the pattern of the conformational forms of mtDNA as assessed in ethidium bromide‐stained gels and by Southern blot analysis of undigested mtDNA. Mammalian mitochondria have three archetypal conformations: form I, supercoiled; form II, open relaxed; and form III, linear [18,19]. Fig.…”

Paradoxical proliferative potential of iron (II) sulphate on cancer cells after the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assay

“…The mitochondrial DNA was markedly damaged after incubating with iron (II) at a concentration of 100 μM for 3 h. It was believed that the major mechanism was the lower level of superoxidase dismutase in rat hepatoma cells when compared with nontransformed cells. Therefore it is believed that iron (II) at a high concentration is cytotoxic towards cancer cells (9).…”

“…In respect to experimental therapeutic cancer research, there are several methodologies that could be employed for the identification of cytotoxic activities, among which colourimetric absorbance assay studies are cheap, simple and convenient strategies, when compared (9). Itoh et al showed that 100 μM iron ions were sufficient to induce cell death, after 3 h of treatment, in murine hepatoma cells, but not in normal murine hepatocytes.…”