Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate.

Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Research Abstract Details 

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Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Abstract Text:

George Quievryn,Joseph Messer,Anatoly Zhitkovich,

Recent epidemiological and risk assessment studies have found a very high risk of lung cancer among chromium(VI)-exposed workers even at permissible levels of exposure. However, mechanistic views on the key genotoxic role of transient Cr(V) intermediates were more consistent with the threshold or highly non-linear (heavy dose) models of genetic damage by intracellular Cr(VI). In this work, we examined the production of mutagenic DNA lesions during metabolism of Cr(VI) by its dominant reducer ascorbate (vitamin C) under conditions promoting increased yield of transient Cr forms. We found that slow reductive activation of Cr(VI) by limited concentrations of ascorbate resulted in a greater yield of DCFH-oxidizing Cr intermediates but these species were unable to cause DNA strand breaks. Cr(VI)-ascorbate reactions generated a high number of Cr-DNA adducts that were responsible for all mutagenic responses detected in Cr(VI)-treated pSP189 shuttle plasmids following their replication in human cells. Mutagenicity of DNA damage resulting from the reactions with increased stability of Cr intermediates was approximately four times lower relative to the conditions lacking detectable Cr(V) formation. Unlike other reactions, slow reduction of Cr(VI) with ascorbate produced Cr-DNA adducts that were more resistant to dissociation by chelators, suggesting multicoordinate binding of Cr(III) to DNA. Overall, our findings do not support the possibility that increased Cr(V) formation at depleted ascorbate levels modeling heavy dose exposures causes higher levels of mutagenic DNA damage.

Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Publishing Authors By Initials

G Quievryn,J Messer,A Zhitkovich,

For similar genetic structures: plasmids research abstracts see: genetic structures: plasmids research

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Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Journal Published:

PUBLICATION TYPE: Research Support, N.I.H., Extr

Journal: Carcinogenesis

VOLUME: 27

Page Numbers: 2316-21

Journal Abbreviation: Carcinogenesis

ISSN: 0143-3334

DAY: 19

MONTH: 05

YEAR: 2006

Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Information

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LANGUAGE: eng

NlmUniqueID: 8008055

Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Keywords Mesh Terms:

KEYWORDS: Plasmids

MESH TERMS: metabolism

Chemical & Substance for Abstract: Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate. Information

Substance Name: Chromium

Registry Number: 7440-47-3

Grant and Affiliation Information for Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate.

AFFILIATION: Department of Pathology and Laboratory Medicine, Brown University, 70 Ship Street, Room 507, Providence RI 02912, USA.

Country: England

AGENCY: United States NIEHS

GRANT: R01 ES008786

ACRONYM: ES

MEDLINETA: Carcinogenesis

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