Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and single-stranded DNA

Douglas Melton, Calvin D. Lewis, Nathan E. Price, Kent S. Gates

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

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. (Chemical Equation Presented).

Original languageEnglish
Pages (from-to)2113-2118
Number of pages6
JournalChemical Research in Toxicology
Volume27
Issue number12
DOIs
StatePublished - Dec 15 2014

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