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Sonochemically induced covalent binding of calf thymus DNA by aziridinylquinones
Antonio E Alegria1, Pedro Sanchez-Cruz, Dalia Lopez-Colon
1Department of Chemistry, University of Puerto Rico at Humacao, Humacao, Puerto Rico 00791. ae_alegria@webmail.uprh.edu
Abstract:
Sonolysis of argon- or oxygen-containing samples in the presence of calf thymus DNA and the diaziridinylquinones 2,5-bis-aziridin-1-yl-3,6-dichloro-1,4-benzoquinone (AZClQ) and 2,5-bis(carboethoxyamino)-3,6-diaziridinyl-1,4-benzoquinone (AZQ) produced quinone-DNA covalent adducts at pH 5.5 and to a much lesser extent at pH 7.4. The corresponding semiquinone derivatives are detected using EPR spectroscopy after sonolysis of argon-saturated solutions at pH 7.4. The amount of covalent adducts decreases with addition of SOD, indicating a role of superoxide in this process. Addition of oxygen to the purging gas decreased but did not eliminate this covalent adduct. Thus this work suggests a possible synergism between bioreductive quinones and ultrasound in antitumor therapies based on alkylating quinone-DNA adduct formation with potential applications to both hypoxic and normally oxygenated conditions.
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