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

Douglas A. Melton | Zendy; Calvin D. Lewis | Zendy; Nathan E. Price | Zendy; Kent S. Gates | Zendy

Open Access

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

Author(s) -

Douglas A. Melton,

Calvin D. Lewis,

Nathan E. Price,

Kent S. Gates

Publication year - 2014

Publication title -

chemical research in toxicology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.031

H-Index - 156

eISSN - 1520-5010

pISSN - 0893-228X

DOI - 10.1021/tx5003657

Subject(s) - dna , adduct , chemistry , covalent bond , dna adduct , covalent binding , ap site , drug , double stranded , dna damage , combinatorial chemistry , biochemistry , biophysics , pharmacology , organic chemistry , biology

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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