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Article ; Online: Role of iron in cancer.

Salnikow, Konstantin

2021 Volume 76, Page(s) 189–194

Abstract: Iron is an essential metal for cellular metabolism. The reduced form of iron is a cofactor in numerous redox reactions in the cell and is therefore required for many vital physiological functions. Since iron is an oxidatively active metal, its ... ...

Abstract	Iron is an essential metal for cellular metabolism. The reduced form of iron is a cofactor in numerous redox reactions in the cell and is therefore required for many vital physiological functions. Since iron is an oxidatively active metal, its homeostasis is tightly regulated in healthy cell. Most of iron exists in a protein-bound form, in erythrocytes as the heme compound hemoglobin, and in storage proteins such as ferritin, hemosiderin and myoglobin. Iron also is bound to proteins and non-heme enzymes involved in oxidation-reduction reactions and the transfer of electrons. There is no free iron inside the cell, however a small fraction of loosely bound iron is found in the cytoplasm. This poorly defined pool of ferrous iron is called labile iron pool. Under pathological conditions iron homeostasis may be disrupted at different levels including absorption, systemic transportation, and cellular uptake and storage. Cancer cells display dysregulated iron homeostasis and, for reasons yet poorly understood, require more iron for their metabolism and growth. As a result, in cancer cells labile iron pool is increased, and loosely bound iron catalyzes Fenton reaction and perhaps other reactions that generate reactive oxygen species. Oxygen-derived free radicals produce DNA mutations, damage proteins and lipids resulting in either cell death or cell transformation.
MeSH term(s)	Animals ; Cell Transformation, Neoplastic/metabolism ; Homeostasis/physiology ; Humans ; Iron/metabolism ; Neoplasms/metabolism ; Neoplasms/pathology
Chemical Substances	Iron (E1UOL152H7)
Language	English
Publishing date	2021-04-24
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	1033980-2
ISSN	1096-3650 ; 1044-579X
ISSN (online)	1096-3650
ISSN	1044-579X
DOI	10.1016/j.semcancer.2021.04.001
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Article: Genetic and epigenetic mechanisms in metal carcinogenesis and cocarcinogenesis: nickel, arsenic, and chromium.

Salnikow, Konstantin / Zhitkovich, Anatoly

Chemical research in toxicology

2007 Volume 21, Issue 1, Page(s) 28–44

Abstract: Chronic exposure to nickel(II), chromium(VI), or inorganic arsenic (iAs) has long been known to increase cancer incidence among affected individuals. Recent epidemiological studies have found that carcinogenic risks associated with chromate and iAs ... ...

Abstract	Chronic exposure to nickel(II), chromium(VI), or inorganic arsenic (iAs) has long been known to increase cancer incidence among affected individuals. Recent epidemiological studies have found that carcinogenic risks associated with chromate and iAs exposures were substantially higher than previously thought, which led to major revisions of the federal standards regulating ambient and drinking water levels. Genotoxic effects of Cr(VI) and iAs are strongly influenced by their intracellular metabolism, which creates several reactive intermediates and byproducts. Toxic metals are capable of potent and surprisingly selective activation of stress-signaling pathways, which are known to contribute to the development of human cancers. Depending on the metal, ascorbate (vitamin C) has been found to act either as a strong enhancer or suppressor of toxic responses in human cells. In addition to genetic damage via both oxidative and nonoxidative (DNA adducts) mechanisms, metals can also cause significant changes in DNA methylation and histone modifications, leading to epigenetic silencing or reactivation of gene expression. In vitro genotoxicity experiments and recent animal carcinogenicity studies provided strong support for the idea that metals can act as cocarcinogens in combination with nonmetal carcinogens. Cocarcinogenic and comutagenic effects of metals are likely to stem from their ability to interfere with DNA repair processes. Overall, metal carcinogenesis appears to require the formation of specific metal complexes, chromosomal damage, and activation of signal transduction pathways promoting survival and expansion of genetically/epigenetically altered cells.
MeSH term(s)	Animals ; Arsenic/toxicity ; Carcinogens/toxicity ; Chromium/toxicity ; Cocarcinogenesis ; DNA/genetics ; Humans ; Metals/toxicity ; Neoplasms/chemically induced ; Neoplasms/genetics ; Nickel/toxicity
Chemical Substances	Carcinogens ; Metals ; Chromium (0R0008Q3JB) ; Nickel (7OV03QG267) ; DNA (9007-49-2) ; Arsenic (N712M78A8G)
Language	English
Publishing date	2007-10-30
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	639353-6
ISSN	1520-5010 ; 0893-228X
ISSN (online)	1520-5010
ISSN	0893-228X
DOI	10.1021/tx700198a
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Article ; Online: A path to translation: How 3D patient tumor avatars enable next generation precision oncology.

Bose, Shree / Barroso, Margarida / Chheda, Milan G / Clevers, Hans / Elez, Elena / Kaochar, Salma / Kopetz, Scott E / Li, Xiao-Nan / Meric-Bernstam, Funda / Meyer, Clifford A / Mou, Haiwei / Naegle, Kristen M / Pera, Martin F / Perova, Zinaida / Politi, Katerina A / Raphael, Benjamin J / Robson, Paul / Sears, Rosalie C / Tabernero, Josep /

Tuveson, David A / Welm, Alana L / Welm, Bryan E / Willey, Christopher D / Salnikow, Konstantin / Chuang, Jeffrey H / Shen, Xiling

Cancer cell

2022 Volume 40, Issue 12, Page(s) 1448–1453

Abstract: 3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs ... ...

Abstract	3D patient tumor avatars (3D-PTAs) hold promise for next-generation precision medicine. Here, we describe the benefits and challenges of 3D-PTA technologies and necessary future steps to realize their potential for clinical decision making. 3D-PTAs require standardization criteria and prospective trials to establish clinical benefits. Innovative trial designs that combine omics and 3D-PTA readouts may lead to more accurate clinical predictors, and an integrated platform that combines diagnostic and therapeutic development will accelerate new treatments for patients with refractory disease.
MeSH term(s)	Humans ; Neoplasms/genetics ; Neoplasms/therapy ; Neoplasms/diagnosis ; Precision Medicine ; Prospective Studies ; Medical Oncology
Language	English
Publishing date	2022-10-20
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2022.09.017
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Zs.A 5650: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article: Ascorbate depletion: a critical step in nickel carcinogenesis?

Salnikow, Konstantin / Kasprzak, Kazimierz S

Environmental health perspectives

2005 Volume 113, Issue 5, Page(s) 577–584

Abstract: Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. ... ...

Abstract	Nickel compounds are known to cause respiratory cancer in humans and induce tumors in experimental animals. The underlying molecular mechanisms may involve genotoxic effects; however, the data from different research groups are not easy to reconcile. Here, we challenge the common premise that direct genotoxic effects are central to nickel carcinogenesis and probably to that of other metals. Instead, we propose that it is formation of metal complexes with proteins and other molecules that changes cellular homeostasis and provides conditions for selection of cells with transformed phenotype. This is concordant with the major requirement for nickel carcinogenicity, which is prolonged action on the target tissue. If DNA is not the main nickel target, is there another unique molecule that can be attacked with carcinogenic consequences? Our recent observations indicate that ascorbate may be such a molecule. Nickel depletes intracellular ascorbate, which leads to the inhibition of cellular hydroxylases, manifested by the loss of hypoxia-inducible factor (HIF)-1alpha and -2alpha hydroxylation and hypoxia-like stress. Proline hydroxylation is crucial for collagen and extracellular matrix assembly as well as for assembly of other protein molecules that have collagen-like domains, including surfactants and complement. Thus, the depletion of ascorbate by chronic exposure to nickel could be deleterious for lung cells and may lead to lung cancer. Key words: ascorbate, carcinogenesis, collagens, extracellular matrix, hypoxia-inducible transcription factor, metals, nickel, protein hydroxylation.
MeSH term(s)	Animals ; Antioxidants/metabolism ; Ascorbic Acid/metabolism ; Cell Transformation, Neoplastic ; DNA Damage ; Homeostasis ; Humans ; Hydroxylation ; Lung Neoplasms/chemically induced ; Lung Neoplasms/physiopathology ; Nickel/metabolism ; Nickel/toxicity ; Proline/metabolism ; Protein Binding ; Rats
Chemical Substances	Antioxidants ; Nickel (7OV03QG267) ; Proline (9DLQ4CIU6V) ; Ascorbic Acid (PQ6CK8PD0R)
Language	English
Publishing date	2005-05
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	195189-0
ISSN	1552-9924 ; 0091-6765 ; 1078-0475
ISSN (online)	1552-9924
ISSN	0091-6765 ; 1078-0475
DOI	10.1289/ehp.7605
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Zs.B 1360: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MO 379: Show issues

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Article: HIF-1: an oxygen and metal responsive transcription factor.

Maxwell, Patrick / Salnikow, Konstantin

Cancer biology & therapy

2004 Volume 3, Issue 1, Page(s) 29–35

Abstract: Normal development and function of metazoan organisms depend on oxygen availability. The level of oxygen can be sensed by individual cells, which respond to reduced oxygenation (hypoxia) largely through activation of hypoxia-inducible factor-1 (HIF-1). ... ...

Abstract	Normal development and function of metazoan organisms depend on oxygen availability. The level of oxygen can be sensed by individual cells, which respond to reduced oxygenation (hypoxia) largely through activation of hypoxia-inducible factor-1 (HIF-1). At the organism level the response to hypoxia involves an increase in red blood cell production. Within tissues, HIF activation increases the blood supply and blood vessel growth. At the individual cell level it is manifested as an increase in anaerobic metabolism in order to sustain basic cellular functions. Iron is central to the oxygen sensing mechanism, and sensitivity to other metals, namely cobalt and nickel, is a distinctive feature of the HIF system; in fact, this is often used as an initial way of implicating HIF-1 in a biological response. Historically, the fact that nickel or cobalt mimicked hypoxia provided an important clue as to the nature of the oxygen sensing mechanism. It also raises the possibility that nickel or cobalt exposure may have important toxic and pathological effects mediated by HIF activation. Here we review the implications of the metal sensitivity of the HIF-1 system, and examine the hypothesis that HIF-1 activation may play an important role in metal induced carcinogenesis.
MeSH term(s)	Animals ; Carcinogens ; Cell Hypoxia ; Cell Transformation, Neoplastic ; Cobalt/toxicity ; DNA-Binding Proteins/metabolism ; Enzymes/metabolism ; Humans ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Neoplasms/genetics ; Neoplasms/physiopathology ; Nickel/toxicity ; Nuclear Proteins/metabolism ; Oxygen Consumption ; Transcription Factors/metabolism ; Transcription, Genetic
Chemical Substances	Carcinogens ; DNA-Binding Proteins ; Enzymes ; HIF1A protein, human ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Nuclear Proteins ; Transcription Factors ; Cobalt (3G0H8C9362) ; Nickel (7OV03QG267)
Language	English
Publishing date	2004-01-10
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2146305-0
ISSN	1538-4047
ISSN	1538-4047
DOI	10.4161/cbt.3.1.547
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Zs.A 5887: Show issues

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Article: Backing into cancer: effects of arsenic on cell differentiation.

Salnikow, Konstantin / Cohen, Mitchell D

Toxicological sciences : an official journal of the Society of Toxicology

2002 Volume 65, Issue 2, Page(s) 161–163

MeSH term(s)	Animals ; Arsenic/toxicity ; Carcinogens/toxicity ; Cell Differentiation/drug effects ; Cell Division/drug effects ; Cells, Cultured ; Gene Expression Regulation, Neoplastic ; Humans
Chemical Substances	Carcinogens ; Arsenic (N712M78A8G)
Language	English
Publishing date	2002-02
Publishing country	United States
Document type	Comment ; Journal Article ; Review
ZDB-ID	1420885-4
ISSN	1096-0929 ; 1096-6080
ISSN (online)	1096-0929
ISSN	1096-6080
DOI	10.1093/toxsci/65.2.161
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Article: Effect of nickel and iron co-exposure on human lung cells.

Salnikow, Konstantin / Li, Xiaomei / Lippmann, Morton

Toxicology and applied pharmacology

2004 Volume 196, Issue 2, Page(s) 258–265

Abstract: Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The ...

Abstract	Exposure to ambient air particulate matter (PM) is associated with increased mortality and morbidity in susceptible populations. The epidemiological data also suggest a relationship between PM air pollution and impairment of cardiopulmonary function. The mechanisms that may be responsible for these effects are not fully understood and are likely related to perturbations of cellular and molecular functions. One type of PM, residual oil fly ash (ROFA), is of particular interest. ROFA does not contain much organic material, but does contain relatively high quantities of transition metals, predominantly nickel, vanadium, and iron, as well as black carbon and sulfates. In this study, we investigated the effect of two metals (iron and nickel) on the induction of "hypoxia-like" stress and the production of interleukins (ILs) in minimally transformed human airway epithelial cells (1HAEo(-)). We found that exposure to soluble nickel sulfate results in the induction of hypoxia-inducible genes and IL-8 production by the 1HAEo(-) cells. The simultaneous addition of iron in either ferric or ferrous form and nickel completely inhibited IL-8 production and had no effect on "hypoxia-like" stress caused by nickel, suggesting the existence of two different pathways for the induction "hypoxia-like" stress and IL-8 production. The effect of nickel was not related to the blocking of iron entry into cells since the level of intracellular iron was not affected by co-exposure with nickel. The obtained data indicate that nickel can induce different signaling pathways with or without interference with iron metabolism. Our observations suggest that in some cases the excess of iron in PM can cancel the effects of nickel.
MeSH term(s)	Air Pollutants/toxicity ; Blotting, Western ; Carbon/toxicity ; Cell Cycle Proteins/biosynthesis ; Chlorides ; Coal Ash ; Deferoxamine/pharmacology ; Epithelial Cells/drug effects ; Epithelial Cells/metabolism ; Ferric Compounds/pharmacokinetics ; Ferric Compounds/toxicity ; Humans ; Hypoxia/chemically induced ; Hypoxia/pathology ; Interleukin-8/antagonists & inhibitors ; Interleukin-8/biosynthesis ; Interleukin-8/secretion ; Intracellular Signaling Peptides and Proteins ; Iron Chelating Agents/pharmacology ; Lung/drug effects ; Lung/metabolism ; Lung/secretion ; Nickel/toxicity ; Particulate Matter
Chemical Substances	Air Pollutants ; Cell Cycle Proteins ; Chlorides ; Coal Ash ; Ferric Compounds ; Interleukin-8 ; Intracellular Signaling Peptides and Proteins ; Iron Chelating Agents ; N-myc downstream-regulated gene 1 protein ; Particulate Matter ; nickel sulfate (4FLT4T3WUN) ; Carbon (7440-44-0) ; Nickel (7OV03QG267) ; Deferoxamine (J06Y7MXW4D) ; ferric chloride (U38V3ZVV3V)
Language	English
Publishing date	2004-04-15
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	204477-8
ISSN	1096-0333 ; 0041-008X
ISSN (online)	1096-0333
ISSN	0041-008X
DOI	10.1016/j.taap.2004.01.003
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Article: Molecular mechanisms of nickel carcinogenesis: gene silencing by nickel delivery to the nucleus and gene activation/inactivation by nickel-induced cell signaling.

Costa, Max / Yan, Yan / Zhao, Daoji / Salnikow, Konstantin

Journal of environmental monitoring : JEM

2003 Volume 5, Issue 2, Page(s) 222–223

Abstract: We have summarized the molecular and cellular events involved in nickel (Ni) compound induced carcinogenesis. The major hypothesis for nickel carcinogenic action has involved the ability of the Ni compound to deliver high concentrations of Ni ... ...

Abstract	We have summarized the molecular and cellular events involved in nickel (Ni) compound induced carcinogenesis. The major hypothesis for nickel carcinogenic action has involved the ability of the Ni compound to deliver high concentrations of Ni intracellularly, enter the nucleus and interact with chromatin. Ni has been found to selectively damage heterochromatin, and a major action of Ni is its ability to silence the expression of genes located near heterochromatin by inducing a loss of histone H4 and H3 acetylation and DNA hypermethylation. When Ni silences critical genes, such as tumor suppressor genes, the cell is altered to a greater state of neoplastic transformation. The carcinogenic hazard of Ni compounds has been directly related to the ability of that Ni compound to raise the intracellular Ni ions. The mechanisms of Ni-induced gene silencing will be discussed. However, recently it has been found that soluble Ni ions can interact with the cell surface receptors and activate cell signaling resulting in the induction of a variety of cellular genes. In particular, the Ca and hypoxia inducible factor pathway is activated in all cells exposed to soluble Ni ions. In the case of HIF-1 induction, a cell is now equipped with the expression of a variety of genes that will allow the cell to survive the lack of oxygen and thus should enable a previously initiated cancer cell to progress into a full malignant state and metastasize. These new findings support the view that soluble Ni ions exhibit carcinogenic potential by activating cell promotion and lend strength to the epidemiological data showing soluble Ni to be associated with cancer risk in Ni refinery workers.
MeSH term(s)	Calcium Signaling ; Cell Transformation, Neoplastic ; Chromatin/drug effects ; Chromatin/physiology ; DNA Damage ; DNA Methylation ; DNA-Binding Proteins/drug effects ; Disease Progression ; Humans ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Neoplasms/etiology ; Neoplasms/physiopathology ; Nickel/adverse effects ; Nuclear Proteins/drug effects ; Risk Assessment ; Signal Transduction ; Transcription Factors
Chemical Substances	Chromatin ; DNA-Binding Proteins ; HIF1A protein, human ; Hypoxia-Inducible Factor 1 ; Hypoxia-Inducible Factor 1, alpha Subunit ; Nuclear Proteins ; Transcription Factors ; Nickel (7OV03QG267)
Language	English
Publishing date	2003-04-08
Publishing country	England
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
ZDB-ID	1453583-x
ISSN	1464-0333 ; 1464-0325
ISSN (online)	1464-0333
ISSN	1464-0325
DOI	10.1039/b210260a
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Article: Hypoxia inducible factor-1 alpha-independent suppression of aryl hydrocarbon receptor-regulated genes by nickel.

Davidson, Todd / Salnikow, Konstantin / Costa, Max

Molecular pharmacology

2003 Volume 64, Issue 6, Page(s) 1485–1493

Abstract: Aryl hydrocarbon receptor (AhR)-dependent enzymes are involved in the biotransformation of harmful xenobiotics into more easily excretable metabolites. Cross-talk between the AhR pathway and the hypoxia inducible factor-1alpha (HIF-1alpha) pathway has ... ...

Abstract	Aryl hydrocarbon receptor (AhR)-dependent enzymes are involved in the biotransformation of harmful xenobiotics into more easily excretable metabolites. Cross-talk between the AhR pathway and the hypoxia inducible factor-1alpha (HIF-1alpha) pathway has been demonstrated previously, although the mechanism remains unclear and quite controversial. Because nickel is known to mimic hypoxia, we investigated the effects of short-term nickel exposure on AhR-dependent gene expression. Gene-chip analysis identified several AhR-dependent genes that are suppressed by exposure to nickel. Using Northern blots, we then confirmed that nickel can down-regulate both the basal and benzo[a]pyrene-inducible expression of AhR-dependent genes in mouse and human cell lines. Using a HIF-1alpha knockout cell line and 3-[2-[4-(bis-(4-fluorophenyl) methylene]-1-piperidinyl)ethyl]-2,3-dihydro-2-thioxo-4(1H)quinazolinone (R59949), which blocks HIF-1alpha protein accumulation, we show HIF-1alpha-independent suppression of AhR-dependent genes by nickel. Desferrioxamine and hypoxia were also able to suppress the basal and inducible expression levels of AhR-regulated genes. Finally, dimethyloxalylglycine, an inhibitor of Fe(II)- and 2-oxoglutarate-dependent dioxygenases also inhibited AhR-dependent expression in a HIF-1alpha-independent manner. Our data suggest that an Fe(II)-, oxoglutarate-, and oxygen-dependent enzyme may directly or indirectly be involved in the regulation of AhR-dependent transcriptional activity by nickel and other hypoxia-mimicking agents.
MeSH term(s)	Animals ; Down-Regulation/drug effects ; Down-Regulation/physiology ; Hypoxia/metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nickel/pharmacology ; Receptors, Aryl Hydrocarbon/antagonists & inhibitors ; Receptors, Aryl Hydrocarbon/biosynthesis ; Receptors, Aryl Hydrocarbon/genetics ; Transcription Factors/biosynthesis ; Transcription Factors/deficiency ; Transcription Factors/genetics ; Transcription Factors/physiology
Chemical Substances	Hypoxia-Inducible Factor 1, alpha Subunit ; Receptors, Aryl Hydrocarbon ; Transcription Factors ; Nickel (7OV03QG267)
Language	English
Publishing date	2003-12
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	124034-1
ISSN	1521-0111 ; 0026-895X
ISSN (online)	1521-0111
ISSN	0026-895X
DOI	10.1124/mol.64.6.1485
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Article: Nickel carcinogenesis.

Kasprzak, Kazimierz S / Sunderman, F William / Salnikow, Konstantin

Mutation research

2003 Volume 533, Issue 1-2, Page(s) 67–97

Abstract: Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, has the potential to produce a variety of pathologic effects. Among them are skin allergies, lung fibrosis, and cancer of ... ...

Abstract	Human exposure to highly nickel-polluted environments, such as those associated with nickel refining, electroplating, and welding, has the potential to produce a variety of pathologic effects. Among them are skin allergies, lung fibrosis, and cancer of the respiratory tract. The exact mechanisms of nickel-induced carcinogenesis are not known and have been the subject of numerous epidemiologic and experimental investigations. These mechanisms are likely to involve genetic and epigenetic routes. The present review provides evidence for the genotoxic and mutagenic activity of Ni(II) particularly at high doses. Such doses are best delivered into the cells by phagocytosis of sparingly soluble nickel-containing dust particles. Ni(II) genotoxicity may be aggravated through the generation of DNA-damaging reactive oxygen species (ROS) and the inhibition of DNA repair by this metal. Broad spectrum of epigenetic effects of nickel includes alteration in gene expression resulting from DNA hypermethylation and histone hypoacetylation, as well as activation or silencing of certain genes and transcription factors, especially those involved in cellular response to hypoxia. The investigations of the pathogenic effects of nickel greatly benefit from the understanding of the chemical basis of Ni(II) interactions with intracellular targets/ligands and oxidants. Many pathogenic effects of nickel are due to the interference with the metabolism of essential metals such as Fe(II), Mn(II), Ca(II), Zn(II), or Mg(II). Research in this field allows for identification of putative Ni(II) targets relevant to carcinogenesis and prediction of pathogenic effects caused by exposure to nickel. Ultimately, the investigations of nickel carcinogenesis should be aimed at the development of treatments that would inhibit or prevent Ni(II) interactions with critical target molecules and ions, Fe(II) in particular, and thus avert the respiratory tract cancer and other adverse health effects in nickel workers.
MeSH term(s)	Air Pollutants ; Animals ; Carcinogens/toxicity ; Cell Transformation, Neoplastic ; Cells, Cultured ; DNA Damage ; Humans ; Mutagens/toxicity ; Neoplasms/chemically induced ; Nickel/toxicity ; Reactive Oxygen Species
Chemical Substances	Air Pollutants ; Carcinogens ; Mutagens ; Reactive Oxygen Species ; Nickel (7OV03QG267)
Language	English
Publishing date	2003-10-17
Publishing country	Netherlands
Document type	Journal Article ; Review
ZDB-ID	206607-5
ISSN	1873-135X ; 0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
ISSN (online)	1873-135X
ISSN	0027-5107 ; 1383-5718 ; 0165-1110 ; 0165-1161 ; 0165-7992 ; 0921-8777 ; 0165-1218 ; 1383-5726 ; 0167-8817 ; 0921-8734 ; 1383-5742
DOI	10.1016/j.mrfmmm.2003.08.021
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In stock of ZB MED Bonn / Germany

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Inter-library loan at ZB MED

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In stock of ZB MED Cologne/Königswinter

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In stock of ZB MED Cologne/Königswinter

Order via subito