title: Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and single-stranded DNA.
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.
authors.affiliation: Department of Chemistry, ‡Department of Biochemistry, University of Missouri , 125 Chemistry Building, Columbia, Missouri 65211, United States.
authors.forename: Douglas
authors.initials: D
authors.lastname: Melton
authors.forename: Calvin D
authors.initials: CD
authors.lastname: Lewis
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Price
authors.forename: Kent S
authors.initials: KS
authors.lastname: Gates
mesh_terms: D000959:Antihypertensive Agents / Q000737:chemistry*; D001483:Base Sequence; D004247:DNA / Q000737:chemistry*; D004277:DNA, Single-Stranded / Q000737:chemistry*; D006830:Hydralazine / Q000737:chemistry*; D013058:Mass Spectrometry
chemical_list: D000959:Antihypertensive Agents; D004277:DNA, Single-Stranded; D006830:Hydralazine; D004247:DNA