Mechanisms in nickel genotoxicity: the significance of interactions with DNA repair

Hartwig, Andrea; Krüger, Inès; Beyersmann, Detmar

doi:10.1016/0378-4274(94)90048-5

Cited by 60 publications

(32 citation statements)

References 14 publications

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“…Therefore, experimental Dt and u were found from the tangents to the melting curves at the points corresponding [18] to the end of the transition. Assuming r 21 = 10 -4 , we obtain r 32 = 1.6 6 10 -4 using Equation (4). The cooperativity parameters of the 2 e 1 and 3 e 2 transitions are thus within the same order of magnitude and the different intervals of these transitions are accounted for mainly by their different melting enthalpies As we observed earlier, at high Mn 2+ concentrations equalising the stability of AT and GC pairs, the DNA melting curves have a kink at the point marking the end of melting.…”

Section: Polya/2 Polyumentioning

confidence: 99%

Ni2+ Ion Effect of Conformations on Single-, Double- and Three-Stranded Homopolynucleotides Containing Adenine and Uracil

Sorokin¹,

Valeev

Gladchenko

et al. 2001

Macromol. Biosci.

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Differential UV and visible spectroscopy and thermal denaturation were used to study the interaction of Ni2+ ions with adenosine 5′‐monophosphate (AMP), uridine 5′‐monophosphate (UMP), single‐stranded polyadenylic acid (polyA) and polyuridylic (polyU), double‐stranded polyA/polyU (AU) and three‐stranded polyA/2 polyU (A2U). The coil → helix transition observed in polyA, AU and A2U at room temperature is induced by Ni2+ binding to the oxygen atoms of the phosphate groups which belong to the disordered single‐stranded parts of the polynucleotides. Ni2+ ions coordinate with bases only in individual AMP and single‐stranded polyA. This coordination causes disordering of the helical parts of the strands. The disordered single strands form thermally stable compact particles with effective radii of ˜100 Å. Diagrams of the phase equilibrium between single‐, double‐ and three‐stranded conformations as a function of temperature and Ni2+ concentration have been obtained. The melting ranges of A2U and AU differ considerably, mainly due to different enthalpies of their helix–coil transitions. The behaviour of the transition parameters in the presence of Ni2+ ions agrees with the data obtained from the theory of equilibrium binding. The constants of the Ni2+ binding to AU and A2U are found. The effect of Ni2+ ions upon the thermal stability of AU and A2U is connected mainly with their different binding to multi‐stranded helices and polyU. The end of melting of the double‐stranded AU formed due to the A2U → AU + U transition has the character of a second‐order phase transition.

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Section: Polya/2 Polyumentioning

confidence: 99%

Ni2+ Ion Effect of Conformations on Single-, Double- and Three-Stranded Homopolynucleotides Containing Adenine and Uracil

Sorokin¹,

Valeev

Gladchenko

et al. 2001

Macromol. Biosci.

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“…By interaction with proteins involved in DNA repair Ni ions could lead to co-mutagenicity (see Section 7.2.4.1.) Hartwig et al (1994) showed that Ni(II) interferes with the incision step in nucleotide excision repair in mammalian cells. Ni(II) was able to block the removal of cyclobutane pyrimidine dimers as determined by T4 endonuclease V-sensitive sites in UV-irradiated HeLa cells.…”

Section: Inhibition Of Dna Repairmentioning

confidence: 99%

Scientific Opinion on the risks to public health related to the presence of nickel in food and drinking water

Publication¹

2015

EFS2

118

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EFSA received a request from the Hellenic Food Authority (EFET) for a scientific opinion on the risk to human health from the presence of nickel (Ni) in food, particularly in vegetables. The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) decided to extend the risk assessment also to drinking water. The reproductive and developmental toxicity in experimental animals was selected as the critical effect for the assessment of chronic effects of Ni. A tolerable daily intake of 2.8 µg Ni/kg body weight (b.w.) per day was derived from a lower 95 % confidence limit for a benchmark dose at 10 % extra risk (BMDL 10 ) of 0.28 mg/kg b.w. for post-implantation fetal loss in rats. The current dietary exposure to Ni raises concern when considering the mean and 95th percentile chronic exposure levels for all different age groups. The systemic contact dermatitis (SCD) elicited in Ni-sensitive humans after oral exposure to Ni was selected as the critical effect suitable for the assessment of acute effects of Ni. A lowest BMDL 10 of 1.1 µg Ni/kg b.w. was derived for the incidence of SCD following oral exposure to Ni of human volunteers. The CONTAM Panel applied a margin of exposure (MOE) approach and considered an MOE of 10 to be indicative of a low health concern. The MOEs calculated considering the estimated mean and the 95th percentile acute exposure levels were considerably below 10 for all age groups. Overall, the CONTAM Panel concluded that, at the current levels of acute dietary exposure to Ni, there is a concern that Ni-sensitized individuals may develop eczematous flare-up skin reactions. The CONTAM Panel noted the need for mechanistic studies to assess the human relevance of the effects on reproduction and development observed in experimental animals and for additional studies on human absorption of nickel from food, for example in combination with duplicate diet studies. Following a call for data on Ni levels in food and drinking water (water intended for human consumption and mineral waters), a total of 18 885 food samples and 25 700 drinking water samples were available in the final dataset to estimate dietary exposure to nickel. No speciation data were provided. Samples were collected between 2003 and 2012 in 15 different European countries, with almost 80 % of the total collected in one Member State. The most reported analytical methods were inductively coupled plasma-mass spectrometry (ICP-MS) and atomic absorption spectrometry (AAS), that represented 54 % and 42 % of the methods reported, respectively. The highest sensitivity was reported for the analysis of drinking water with a limit of quantification (LOQ) of 0.001 µg/L (for both ICP-MS and AAS). In food, ICP-MS showed the lowest LOQ for the analysis of 'Alcoholic beverages' (0.002 µg/kg) while the lowest LOQ reported with AAS was 1 µg/kg for samples of 'Fish and seafood' and 'Sugar and confectionery'. In the final dataset, left-censored data represented 66 % of the analytical results, with 35 % in food samples and 89 % in drinking water sa...

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“…Cu 2ϩ and Zn 2ϩ are essential trace elements present in many species (5,6), whereas Ni 2ϩ enters the cell by chronic exposure (7) and is a known carcinogen (8). Copper functions as a cofactor in copper-zinc superoxide dismutase and plays an important role in the defense against oxygen-derived free radicals that have deleterious effects on biological macromolecules (4).…”

mentioning

confidence: 99%

Crystal structures of the copper and nickel complexes of RNase A: Metal-induced interprotein interactions and identification of a novel copper binding motif

Balakrishnan

Ramasubbu

Varughese

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

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We report the crystal structures of the copper and nickel complexes of RNase A. The overall topology of these two complexes is similar to that of other RNase A structures. However, there are significant differences in the mode of binding of copper and nickel. There are two copper ions per molecule of the protein, but there is only one nickel ion per molecule of the protein. Significant changes occur in the interprotein interactions as a result of differences in the coordinating groups at the common binding site around His-105. Consequently, the copper-and nickel-ion-bound dimers of RNase A act as nucleation sites for generating different crystal lattices for the two complexes. A second copper ion is present at an active site residue His-119 for which all the ligands are from one molecule of the protein. At this second site, His-119 adopts an inactive conformation (B) induced by the copper. We have identified a novel copper binding motif involving the ␣-amino group and the N-terminal residues.Metal ions are responsible for a wide range of functions, including nucleophilic catalysis in enzymes such as carbonic anhydrase and carboxypeptidase, electron transfer in proteins such as rubredoxin and the cytochromes, and stabilization of protein structure in many proteins from zinc finger to alcohol dehydrogenase (1, 2) and in gene regulation (3,4). Cu 2ϩ and Zn 2ϩ are essential trace elements present in many species (5, 6), whereas Ni 2ϩ enters the cell by chronic exposure (7) and is a known carcinogen (8). Copper functions as a cofactor in copper-zinc superoxide dismutase and plays an important role in the defense against oxygen-derived free radicals that have deleterious effects on biological macromolecules (4). Because of the many biological roles played by these metal ions, efforts have been recently directed to engineer de novo metal binding sites to impart a desired property to a protein. For example, metal binding sites have been engineered to aid protein purification (9), to enhance protein stability (10, 11) and regulation of catalytic activity (12, 13), and to introduce metal ions into novel protein scaffolds (14,15). In this regard structural studies of metalloproteins have greatly aided in engineering of novel metal binding sites into proteins.However, presence of these transition metals in abnormal levels due to metabolic disorders or due to chronic exposure has been linked to DNA damage and eventually to cell death. For example, for Wilson and Menkes diseases, there is an aberrant copper metabolic pathway leading to copper accumulation (16). In Alzheimer disease, decreased levels of a metallothionein-like protein has been observed leading to an increase in the levels of zinc (17, 18). Inability of metalloproteins to perform normal functions has been directly attributed to the absence of metal ions leading to a conformational change, as shown by crystallographic, spectroscopic, and biochemical studies (19-23). But so far there has been limited evidence to elucidate how metals, upon binding, can forc...

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Mechanisms in nickel genotoxicity: the significance of interactions with DNA repair

Cited by 60 publications

References 14 publications

Ni2+ Ion Effect of Conformations on Single-, Double- and Three-Stranded Homopolynucleotides Containing Adenine and Uracil

Ni2+ Ion Effect of Conformations on Single-, Double- and Three-Stranded Homopolynucleotides Containing Adenine and Uracil

Scientific Opinion on the risks to public health related to the presence of nickel in food and drinking water

Crystal structures of the copper and nickel complexes of RNase A: Metal-induced interprotein interactions and identification of a novel copper binding motif

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