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Disproportionation of a model chromium(V) complex causes extensive chromium(III)-DNA binding in vitro

Levina, Aviva; Lay, Peter; Dixon, Nicholas

Description

The first direct evidence for the role of Cr(V) complexes in the formation of potentially mutagenic Cr(III)-DNA adducts has been obtained. A model complex for the stabilized Cr(V) species formed in Cr(VI)-treated cells, [CrVO(ehba)2]- [ehba = 2-ethyl-2-hydroxybutanoato-(2-)], rapidly disproportionates in HEPES buffers at pH 7.4 [3 Cr(V) → 2 Cr(VI) + Cr(III)], and the formed Cr(III) species undergo efficient ionic binding to DNA, followed by slower covalent binding. The extent of Cr(III)-DNA...[Show more]

dc.contributor.authorLevina, Aviva
dc.contributor.authorLay, Peter
dc.contributor.authorDixon, Nicholas
dc.date.accessioned2015-12-13T23:35:58Z
dc.identifier.issn0893-228X
dc.identifier.urihttp://hdl.handle.net/1885/94168
dc.description.abstractThe first direct evidence for the role of Cr(V) complexes in the formation of potentially mutagenic Cr(III)-DNA adducts has been obtained. A model complex for the stabilized Cr(V) species formed in Cr(VI)-treated cells, [CrVO(ehba)2]- [ehba = 2-ethyl-2-hydroxybutanoato-(2-)], rapidly disproportionates in HEPES buffers at pH 7.4 [3 Cr(V) → 2 Cr(VI) + Cr(III)], and the formed Cr(III) species undergo efficient ionic binding to DNA, followed by slower covalent binding. The extent of Cr(III)-DNA binding significantly exceeds that caused by [CrIII(OH2)6]3+ or by the Cr(III) products of Cr(VI) reductions under similar conditions. The Cr(III)-DNA binding can be dramatically reduced by the ability of the reaction medium (e.g., phosphate buffer) to form complexes with Cr(III) during and after the disproportionation reaction. A mechanism of Cr(III)-DNA binding caused by Cr(V) disproportionation has been proposed on the basis of stoichiometric and kinetic studies.
dc.publisherAmerican Chemical Society
dc.sourceChemical Research in Toxicology
dc.subjectKeywords: butyric acid derivative; chromium derivative; animal cell; article; chemical binding; chemical reaction kinetics; DNA adduct; DNA binding; fish; nonhuman; stoichiometry; Binding Sites; Carcinogens; Chromium; DNA Adducts; DNA Damage; Kinetics; Ligands; Oxi
dc.titleDisproportionation of a model chromium(V) complex causes extensive chromium(III)-DNA binding in vitro
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume14
dc.date.issued2001
local.identifier.absfor030499 - Medicinal and Biomolecular Chemistry not elsewhere classified
local.identifier.ariespublicationMigratedxPub25692
local.type.statusPublished Version
local.contributor.affiliationLevina, Aviva, University of Sydney
local.contributor.affiliationLay, Peter, University of Sydney
local.contributor.affiliationDixon, Nicholas, College of Physical and Mathematical Sciences, ANU
local.description.embargo2037-12-31
local.bibliographicCitation.issue8
local.bibliographicCitation.startpage946
local.bibliographicCitation.lastpage950
local.identifier.doi10.1021/tx010077g
dc.date.updated2015-12-12T09:42:01Z
local.identifier.scopusID2-s2.0-0034868663
CollectionsANU Research Publications

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