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

A. Levina; P. A. Lay; N. E. Dixon

doi:10.1021/tx010077g

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

A. Levina, P. A. Lay^*, N. E. Dixon

^*Corresponding author for this work

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Abstract

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, [Cr^VO(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 [Cr^III(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.

Original language	English
Pages (from-to)	946-950
Number of pages	5
Journal	Chemical Research in Toxicology
Volume	14
Issue number	8
DOIs	https://doi.org/10.1021/tx010077g
Publication status	Published - 2001

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10.1021/tx010077g

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@article{8475062bb77c4badbe278b35e6cbf51d,

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

abstract = "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 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.",

author = "A. Levina and Lay, {P. A.} and Dixon, {N. E.}",

year = "2001",

doi = "10.1021/tx010077g",

language = "English",

volume = "14",

pages = "946--950",

journal = "Chemical Research in Toxicology",

issn = "0893-228X",

publisher = "American Chemical Society",

number = "8",

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TY - JOUR

T1 - Disproportionation of a model chromium(V) complex causes extensive chromium(III)-DNA binding in vitro

AU - Levina, A.

AU - Lay, P. A.

AU - Dixon, N. E.

PY - 2001

Y1 - 2001

N2 - 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 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.

AB - 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 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.

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U2 - 10.1021/tx010077g

DO - 10.1021/tx010077g

M3 - Article

SN - 0893-228X

VL - 14

SP - 946

EP - 950

JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

IS - 8

ER -

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

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