Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA

[Image: see text] Hydralazine (4) is an antihypertensive agent that displays both mutagenic and epigenetic properties. Here, gel electrophoretic, mass spectroscopic, and chemical kinetics methods were used to provide evidence that medicinally relevant concentrations of 4 rapidly form covalent adduct...

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Autores principales: Melton, Douglas, Lewis, Calvin D., Price, Nathan E., Gates, Kent S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2014
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269403/
https://www.ncbi.nlm.nih.gov/pubmed/25405892
http://dx.doi.org/10.1021/tx5003657
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author Melton, Douglas
Lewis, Calvin D.
Price, Nathan E.
Gates, Kent S.
author_facet Melton, Douglas
Lewis, Calvin D.
Price, Nathan E.
Gates, Kent S.
author_sort Melton, Douglas
collection PubMed
description [Image: see text] Hydralazine (4) is an antihypertensive agent that displays both mutagenic and epigenetic properties. Here, gel electrophoretic, mass spectroscopic, and chemical kinetics methods were used to provide evidence that medicinally relevant concentrations of 4 rapidly form covalent adducts with abasic sites in double- and single-stranded DNA under physiological conditions. These findings raise the intriguing possibility that the genotoxic properties of this clinically used drug arise via reactions with an endogenous DNA lesion rather than with the canonical structure of DNA.
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spelling pubmed-42694032015-11-06 Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA Melton, Douglas Lewis, Calvin D. Price, Nathan E. Gates, Kent S. Chem Res Toxicol [Image: see text] Hydralazine (4) is an antihypertensive agent that displays both mutagenic and epigenetic properties. Here, gel electrophoretic, mass spectroscopic, and chemical kinetics methods were used to provide evidence that medicinally relevant concentrations of 4 rapidly form covalent adducts with abasic sites in double- and single-stranded DNA under physiological conditions. These findings raise the intriguing possibility that the genotoxic properties of this clinically used drug arise via reactions with an endogenous DNA lesion rather than with the canonical structure of DNA. American Chemical Society 2014-11-06 2014-12-15 /pmc/articles/PMC4269403/ /pubmed/25405892 http://dx.doi.org/10.1021/tx5003657 Text en Copyright © 2014 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Melton, Douglas
Lewis, Calvin D.
Price, Nathan E.
Gates, Kent S.
Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title_full Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title_fullStr Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title_full_unstemmed Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title_short Covalent Adduct Formation between the Antihypertensive Drug Hydralazine and Abasic Sites in Double- and Single-Stranded DNA
title_sort covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and single-stranded dna
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269403/
https://www.ncbi.nlm.nih.gov/pubmed/25405892
http://dx.doi.org/10.1021/tx5003657
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