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

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• 作者：Douglas Melton ; Calvin D. Lewis ; Nathan E. Price ; Kent S. Gates
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：December 15, 2014
• 年：2014
• 卷：27
• 期：12
• 页码：2113-2118
• 全文大小：266K
• ISSN：1520-5010

文摘

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.