Formation of DNA-protein cross-links in cultured mammalian cells upon treatment with iron ions

Altman, Steven; Zastawny, Tomasz H.; Randers‐Eichhorn, Lisa; Cacciuttolo, Marco A.; Akman, Steven A.; Dizdaroğlu, Miral; Rao, Govind

doi:10.1016/0891-5849(95)00095-f

Cited by 85 publications

(40 citation statements)

References 26 publications

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“…Iron-induced oxidant formation is known to cause DNA strand breaks, DNA-protein cross-links, and activation of protein kinase C; increase the production of heat-shock proteins; and alter calcium homeostasis in cells (Altman et al 1995;Farber 1994;Mello Filho and Meneghini 1984;Meneghini 1997;Stohs and Bagchi 1995). Other recent experiments have also implicated the involvement of iron/transition metals in the effects of electromagnetic fields.…”

Section: Discussionmentioning

confidence: 95%

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Magnetic-field-induced DNA strand breaks in brain cells of the rat.

Lai

Singh

2004

Environ Health Perspect

281

173

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In previous research, we found that rats acutely (2 hr) exposed to a 60-Hz sinusoidal magnetic field at intensities of 0.1-0.5 millitesla (mT) showed increases in DNA single-and double-strand breaks in their brain cells. Further research showed that these effects could be blocked by pretreating the rats with the free radical scavengers melatonin and N-tert-butyl-α-phenylnitrone, suggesting the involvement of free radicals. In the present study, effects of magnetic field exposure on brain cell DNA in the rat were further investigated. Exposure to a 60-Hz magnetic field at 0.01 mT for 24 hr caused a significant increase in DNA single-and double-strand breaks. Prolonging the exposure to 48 hr caused a larger increase. This indicates that the effect is cumulative. In addition, treatment with Trolox (a vitamin E analog) or 7-nitroindazole (a nitric oxide synthase inhibitor) blocked magnetic-field-induced DNA strand breaks. These data further support a role of free radicals on the effects of magnetic fields. Treatment with the iron chelator deferiprone also blocked the effects of magnetic fields on brain cell DNA, suggesting the involvement of iron. Acute magnetic field exposure increased apoptosis and necrosis of brain cells in the rat. We hypothesize that exposure to a 60-Hz magnetic field initiates an iron-mediated process (e.g., the Fenton reaction) that increases free radical formation in brain cells, leading to DNA strand breaks and cell death. This hypothesis could have an important implication for the possible health effects associated with exposure to extremely low-frequency magnetic fields in the public and occupational environments.

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Section: Discussionmentioning

confidence: 95%

“…In another study (Singh and Lai 1998), we found that acute magnetic field exposure induced the formation of DNA-protein and DNA-DNA cross-links in brain cells of rats, which could be the results of free-radical damage involving iron cations (Altman et al 1995;Lloyd et al 1997).…”

mentioning

confidence: 99%

Magnetic-field-induced DNA strand breaks in brain cells of the rat.

Lai

Singh

2004

Environ Health Perspect

281

173

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“…They are capable of scavenging iron released from less stable proteins and converting it to biominerals such as goethite, depositing it as crystals of relatively uniform size, in surrounding tissues. These iron nanoparticles may have stabilized cell architecture and may even be responsible for preserving intracellular components chemically consistent with DNA [22] through iron-mediated DNA-protein cross-links [80].…”

Section: Discussionmentioning

confidence: 99%

A role for iron and oxygen chemistry in preserving soft tissues, cells and molecules from deep time

Schweitzer¹,

et al. 2014

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The persistence of original soft tissues in Mesozoic fossil bone is not explained by current chemical degradation models. We identified iron particles (goethite-aFeO(OH)) associated with soft tissues recovered from two Mesozoic dinosaurs, using transmission electron microscopy, electron energy loss spectroscopy, micro-X-ray diffraction and Fe micro-X-ray absorption nearedge structure. Iron chelators increased fossil tissue immunoreactivity to multiple antibodies dramatically, suggesting a role for iron in both preserving and masking proteins in fossil tissues. Haemoglobin (HB) increased tissue stability more than 200-fold, from approximately 3 days to more than two years at room temperature (258C) in an ostrich blood vessel model developed to test post-mortem 'tissue fixation' by cross-linking or peroxidation. HB-induced solution hypoxia coupled with iron chelation enhances preservation as follows: HB þ O 2 . HB 2 O 2 . 2O 2 þO 2 . The well-known O 2 /haeme interactions in the chemistry of life, such as respiration and bioenergetics, are complemented by O 2 /haeme interactions in the preservation of fossil soft tissues.

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“…Covalent DNA-protein cross-links are formed in cells in vivo or in chromatin in vitro by exposure to free radical-generating systems, e.g., ionising radiation. The formation of a thymine-tyrosine cross-link has been observed in mammalian chromatin in vitro and in living cells upon exposure to ionising radiation, H 2 O 2 , metal ions and carcinogenic compounds [Dizdaroglu et al 1989, Olinski et al, 1992, Altman et al, 1995. The formation mechanism of DNA-protein cross-link has been proposed to involve the addition of the allyl radical of thymine in DNA to tyrosine in a protein, followed by oxidation.…”

Section: Ros-mediated Dna Damagementioning

confidence: 99%