Molecular mechanisms in nickel carcinogenesis: modeling Ni(II) binding site in histone H4.

Zoroddu, Maria Antonietta; Schinocca, Laura; Kowalik-Jankowska, Teresa; Kozłowski, Henryk; Salnikow, Konstantin; Costa, Max

doi:10.1289/ehp.02110s5719

Cited by 56 publications

(43 citation statements)

References 41 publications

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“…Acetylation of lysine 12 and 16 in yeast was more strongly affected than lysine 5 and 8, and it was proposed that nickel binding to histidine 18 in histone H4 may be responsible for this effect (36). The loss of histone acetylation and DNA methylation worked together in gpt gene silencing in G12 transgenic cell line by nickel (32,37).…”

Section: Genetic and Epigenetic Changesmentioning

confidence: 99%

Genetic and Epigenetic Mechanisms in Metal Carcinogenesis and Cocarcinogenesis: Nickel, Arsenic, and Chromium

Salnikow

Zhitkovich

2007

Chem. Res. Toxicol.

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815

539

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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.

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Section: Genetic and Epigenetic Changesmentioning

confidence: 99%

Genetic and Epigenetic Mechanisms in Metal Carcinogenesis and Cocarcinogenesis: Nickel, Arsenic, and Chromium

Salnikow

Zhitkovich

2007

Chem. Res. Toxicol.

Self Cite

815

539

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“…70 71 Nickel binding to the H4 N-terminal peptide at His 18 is thought to interfere with the interaction of histone acetyltransferase complexes (HAT) with chromatin. 72 Other histone modifications that are also globally affected by nickel treatment include H3K9me2, H3K4me3 and ubiquitination of histones H2A and H2B (H2A/H2Bub). 49,60,61,73,74 In some cases, the increase in H2A/H2B ubiquitination has been correlated to upregulation of the Ubiquitin-Conjugating Enzyme H6 (UbcH6) E2 ligase at the protein level or inhibition of an unidentified histone deubiquitinating activity.…”

Section: O N O T D I S T R I B U T Ementioning

confidence: 99%

Environmental epigenetics in metal exposure

2011

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“…The histone H3 motif, -CAIH-is located in a hollow structure of the core histone octamer, while the -TESHHKAKGK motif of histone H2A is positioned near the end of its unstructured C-terminal tail. Nickel coordination is also offered by the -AKRHRK-motif in histone H4, [173] and the -ELAKHAmotif in histone H2B [174]. The sequestration of Ni 2ϩ by histone tetramer (H3/ H4) 2 and histone H2A has been evaluated using numerical models and found to be substantial, even in the presence of maximal physiological concentrations of the major competing cellular ligands histidine and glutathione [158,172,175].…”

Section: Histones and Protaminesmentioning

confidence: 99%