DNA Cleavage and Detection of DNA Radicals Formed from Hydralazine and Copper (II) by ESR and Immuno-Spin Trapping

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• 作者：Birandra K. Sinha ; Fabian Leinisch ; Suchandra Bhattacharjee ; Ronald P. Mason
• 刊名：Chemical Research in Toxicology
• 出版年：2014
• 出版时间：April 21, 2014
• 年：2014
• 卷：27
• 期：4
• 页码：674-682
• 全文大小：390K
• 年卷期：v.27,no.4(April 21, 2014)
• ISSN：1520-5010

文摘

Metal ion-catalyzed oxidation of hydrazine and its derivatives leads to the formation of the hydrazyl radical and subsequently to oxy-radicals in the presence of molecular oxygen. Here, we have examined the role of Cup>2+p>-catalyzed oxidation of hydralazine in the induction of DNA damage. Neither 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) nor dimethyl sulfoxide (DMSO) was effective in inhibiting hydralazine-Cup>2+p>-induced DNA damage. Singlet oxygen did not appear to participate in this DNA cleavage. The one-electron oxidation of hydralazine also leads to the formation of DNA radicals as confirmed by immuno-spin trapping with 5,5-dimethyl-1-pyrroline-N-oxide. Electron spin resonance (ESR) and spin-trapping studies further confirmed the formation of DNA radicals; predominantly, 2鈥?deoxyadenosine radical adducts were detected, while some radicals were also detected with other nucleosides. Our results suggest that free hydroxyl radicals may not be the main damaging species causing DNA cleavage and that possibly Cu-peroxide complexes, formed from Cup>+p>-H₂O₂, are responsible for this hydralazine-Cup>2+p>-induced DNA cleavage.