Separation and characterization of oxaliplatin dinucleotides from DNA using HPLC-ESI ion trap mass spectrometry

Analytical and Bioanalytical Chemistry
Shereen Mowaka, Michael Linscheid

Abstract

Oxaliplatin is a third-generation platinum complex, and has a broad spectrum of antitumor activity. Such platinum complexes with the DACH carrier ligand have recently received increasing attention since they show efficacy against cisplatin-resistant cell lines. As the foremost indication of antitumor activity of platinum drugs is the formation of adducts with genomic DNA, calf thymus DNA-oxaliplatin adducts were the major target in this study. Calf thymus DNA was incubated with oxaliplatin, resulting in the formation of a large number of platinum-DNA adducts. Treated DNA was digested into the dinucleotides with a combination of enzymes, namely, benzonase, alkaline phosphatase, and nuclease S1. Using a high-performance liquid chromatography, we carried out the separation of individual platinum-DNA adducts which were concurrently identified using electrospray ionization ion trap mass spectrometry (MS). Both 1,2-intrastrand and 1,2-interstrand cross-linked adducts were found; however, those of the intrastrand nature have a considerably higher abundance than those of the interstrand cross-links. Among them, d(GpG)-oxaliplatin was the most abundant bifuctional adduct. To a lesser extent, a few monofunctional adducts were detected as...Continue Reading

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Citations

Oct 5, 2011·Cancer Chemotherapy and Pharmacology·C L KingM Barbier
Aug 23, 2011·Metallomics : Integrated Biometal Science·Aref ZayedBarry L Sharp
Sep 19, 2012·Metallomics : Integrated Biometal Science·Matthias ZieheMichael W Linscheid
Sep 29, 2012·Journal of Mass Spectrometry : JMS·Shereen MowakaMichael W Linscheid
Jul 23, 2009·Chemical Research in Toxicology·Dalia MohamedMichael W Linscheid

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