Evidence that iron-overload promotes 7, 12-dimethylbenz(a)anthracene-induced skin tumorigenesis in mice

Rezazadeh, Hassan; Athar, Mohammad

doi:10.1080/13510002.1997.11747127

Cited by 24 publications

(19 citation statements)

References 27 publications

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“…Skin in parenteral iron overload Tissue distribution of iron in secondary hemochromatosis can differ significantly from that in the common form of hereditary hemochromatosis (Andrews, 1999), and parenteral injections of iron have been used to demonstrate toxic effects of iron in skin (Rezazadeh and Athar, 1997;Bhasin et al, 2003). Hairless animals were given repeated intraperitoneal injections of iron dextran, and after several weeks iron was measured in the epidermis, dermis, and several internal organs.…”

Section: Figurementioning

confidence: 99%

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Adams

Lazova

Andrews

et al. 2005

Journal of Investigative Dermatology

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In human hemochromatosis, tissue toxicity is a function of tissue iron levels. Despite reports of skin toxicity in hemochromatosis, little is known about iron levels in skin of individuals with systemic iron overload. We measured skin iron and studied skin histology in three mouse models of systemic iron overload: mice with a deletion of the hemochromatosis (Hfe) gene, mice fed a high iron diet, and mice given parenteral injections of iron. In Hfe(-/-) mice, iron content in the epidermis and dermis was unexpectedly the same as in Hfe(+/+) mice, and there were no histological abnormalities detected after 30 wk. A high iron diet produced increased iron in the epidermis of both normal and Hfe(-/-) animals; a high diet increased iron in the dermis only in Hfe(-/-) mice. Increased skin iron was not associated with other histological changes, even after 19 wk. Parenteral administration of iron produced increased iron in the epidermis and dermis, and gave the skin a bronze hue. These results show that the amount and distribution of iron in the skin depends on the etiology of iron overload. It appears that neither Hfe deletion nor elevated skin iron alone can account for cutaneous manifestations reportedly seen in humans with hereditary hemochromatosis.

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Section: Figurementioning

confidence: 99%

Iron in Skin of Mice with Three Etiologies of Systemic Iron Overload

Adams

Lazova

Andrews

et al. 2005

Journal of Investigative Dermatology

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“…Mobilisable iron increases the production of oxygen free radicals (Barbouti et al 2001) and promotes tumorigenesis (Rezazadeh and Athar 1997;Rezazadeh et al 2005). Mobilisable copper also causes oxidative damage (Ferretti et al 2003) and promotes angiogenesis (Finney et al 2009;Xie and Kang 2009).…”

Section: Introductionmentioning

confidence: 97%

Influence of zinc and zinc chelator on HT-29 colorectal cell line

et al. 2010

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Trace elements are involved in many key pathways involving cell cycle control. The influence of zinc and zinc chelator (TPEN) on transcription levels of the main zinc transporters (ZnT1 and ZIP1) in the HT-29 colorectal cell line has not been reported. Proliferation of HT-29 cells was measured using the methylene blue assay after exposure to zinc (two concentrations), TPEN (two concentrations), or a combination of zinc and TPEN (simultaneously and sequentially) for 4 h, 8 h, and 24 h. The transcription levels of ZnT1, ZIP1, vascular endothelial growth factor (VEGF), and caspase-3 were determined using reverse transcriptase real-time polymerase chain reaction (RT-PCR) after exposure of cells to zinc and TPEN. The zinc content in the substrate (medium used for culture) was determined using atomic absorption spectrometry. TPEN decreased cellular proliferation causing complete cell death by 8 h. Zinc had a protective effect against short periods of exposure to TPEN. There was no correlation between the transcripts of main zinc transporters and the zinc content in the substrate. The zinc content in the substrate remained constant after varying periods of cell culture. TPEN decreased the transcript levels of caspase-3 and VEGF, which are surrogate markers for apoptosis and angiogenesis. Zinc chelation of HT-29 cells causes cell death. Zinc appears to be protective for short periods of exposure to TPEN but has no protective effect on prolonged exposure. HT-29 cells are not able to counteract the effect of intracellular chelation of zinc by altering zinc transport. Further research into the mechanisms of these findings is necessary and may lead to novel therapeutic options.

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“…The mechanism of iron contributing to carcinogenesis has not been determined. Possible mechanisms include the important role of iron in the production of free oxygen radicals [37], causing secondary damage to nucleic acids [38], thereby inducing [39] and promoting [40][41][42] carcinogenesis. Various iron chelators have antiproliferative activity on hepatoma cell lines [43][44][45][46].…”

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confidence: 99%