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Updated: Apr 20, 2026

Formation of Covalent DNA Adducts by Enzymatically Activated Carcinogens and Drugs In Vitro and Their Determination by 32P-postlabeling
Published on: March 20, 2018
Covalent adduct formation between the antihypertensive drug hydralazine and abasic sites in double- and
Douglas Melton1, Calvin D Lewis, Nathan E Price
1Department of Chemistry, ‡Department of Biochemistry, University of Missouri , 125 Chemistry Building, Columbia, Missouri 65211, United States.
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.
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