Speciation of oxaliplatin adducts with DNA nucleotides

Zayed, Aref; Jones, George D.D.; Reid, Helen J.; Shoeib, Tamer; Taylor, S.E.; Thomas, Anne; Wood, Joanna; Sharp, Barry L.

doi:10.1039/c1mt00041a

Cited by 36 publications

(32 citation statements)

References 44 publications

(50 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These adducts were also characterized with UV absorption data and SF‐ICP‐MS elemental 195 Pt and 31 P signals. Further, interaction of oxaliplatin with AG and GG di‐nucleotides resulted in the formation of three adducts: DACHPt‐GG and two isomers of the DAC (Zayed et al, ) DACHPt‐AG adduct was confirmed with ESI‐MS and complementary data obtained from UV and SF‐ICP‐MS. An LC‐ICP‐MS method to quantify oxaliplatin GG intra‐strand adducts (DACHPt‐GG) was developed and used to monitoring the in vitro formation and repair of these adducts in human colorectal cancer cells.…”

Section: Dna Adduct Analysismentioning

confidence: 83%

Mass spectrometry analysis of nucleosides and nucleotides

Dudley

Bond

2013

Mass Spec Rev

View full text Add to dashboard Cite

Mass spectrometry has been widely utilised in the study of nucleobases, nucleosides and nucleotides as components of nucleic acids and as bioactive metabolites in their own right. In this review, the application of mass spectrometry to such analysis is overviewed in relation to various aspects regarding the analytical mass spectrometric and chromatographic techniques applied and also the various applications of such analysis.

show abstract

Section: Dna Adduct Analysismentioning

confidence: 83%

Mass spectrometry analysis of nucleosides and nucleotides

Dudley

Bond

2013

Mass Spec Rev

View full text Add to dashboard Cite

show abstract

“…Under the specific conditions of this experiment, cisplatin produces 1–5 adducts per 10 6 DNA nucleotides, a level of modification typically observed in cisplatin-treated cells and in DNA isolated from clinical samples. 14, 15 Compound 1 produced irreversible damage with DNA at a significantly higher frequency of up to 25 adducts per 10 6 nucleotides. Likewise, compound 1 showed considerably more efficient DNA binding in experiments in which NCI-H460 cells were incubated with compound 1 and cisplatin for 12 h, but at their respective 90% inhibitory concentrations (IC 90 values were 94 nM for compound 1 vs. 11 μM for cisplatin, determined in 72-h incubations).…”

Section: Resultsmentioning

confidence: 99%

Analysis of the DNA damage produced by a platinum–acridine antitumor agent and its effects in NCI-H460 lung cancer cells

et al. 2012

View full text Add to dashboard Cite

High-performance liquid chromatography in conjunction with electrospray mass spectrometry (LC-ESMS) was used to structurally characterize the adducts formed by the platinum–acridine agent [PtCl(en)(N-(2-(acridin-9-ylamino)ethyl)-N-methylpropionimidamide)](NO3)2 (compound 1) in cell-free DNA. Compound 1 forms monofunctional adducts exclusively with guanine, based on the fragments identified in enzymatic digests (dG*, dGMP*, dApG*, and dTpG*, where the asterisk denotes bound drug). The time course of accumulation and DNA adduct formation of compound 1 and the clinical drug cisplatin in NCI-H460 lung cancer cells at physiologically relevant drug concentrations (0.1 μM) was studied by inductively-coupled plasma mass spectrometry (ICP-MS). Compound 1 accumulates rapidly in cells and reaches intracellular levels of up to 60-fold higher than those determined for cisplatin. The hybrid agent shows unusually high DNA binding levels: while cisplatin adducts form at a maximum frequency of 5 adducts per 106 nucleotides, compound 1 produces 25 adducts per 106 nucleotides after only 3 h of continuous incubation with the lung cancer cells. The high overall levels of compound 1 in the cells and in cellular DNA over the entire 12-h treatment period translate into a rapid decrease in cell viability. Possible implications of these findings for the mechanism of action of compound 1 and the agent’s potential to overcome tumor resistance to cisplatin are discussed.

show abstract

“…For quantification at levels below the ESI detection limit, LC/ICP‐MS monitoring of platinum content has been established; the reliable quantification of DNA adducts is under scrutiny right now.…”

Section: Resultsmentioning

confidence: 99%

Structures of oxaliplatin‐oligonucleotide adducts from DNA

et al. 2012

View full text Add to dashboard Cite

Oxaliplatin, [(1R,2R)-cyclohexane-1,2-diamine](ethanedioato-O,O')platinum(II) shows a great efficiency against colorectal cancer. Although the mode of action of oxaliplatin is not yet understood, it is commonly accepted that binding of oxaliplatin to DNA prevents DNA synthesis and alters protein to DNA binding. In order to elucidate the modified DNA-protein interaction and thus to understand the mechanisms leading to cellular misinterpretation of DNA information and apoptosis, we have identified the preferential binding sites and the dynamics of the oxaliplatin-DNA intrastrand and interstrand adducts at the oligomer level using high-performance liquid chromatography/electrospray ionization-tandem mass spectrometry (HPLC/ESI-MS/MS) and HPLC/inductively coupled plasma-MS for quantitative studies. We used a combination of benzonase, alkaline phosphatase and Nuclease S1 for digestion. This digestion procedure allows the study of platinated oligomeric nucleotides and more complex interstrand adducts. The digestion products were mostly chromatographically separated and characterized using HPLC/ESI-ion trap MS/MS experiments. We could show that the adducts to guanine and adenine are quite dynamic; that is, the ratios are changing for several days. In addition, the resulting adducts provide evidence for the action of the digesting enzymes and indicate that the adduct spectrum at the oligomeric level is different to that at the commonly studies dinucleotide level.

show abstract

Speciation of oxaliplatin adducts with DNA nucleotides

Cited by 36 publications

References 44 publications

Mass spectrometry analysis of nucleosides and nucleotides

Mass spectrometry analysis of nucleosides and nucleotides

Analysis of the DNA damage produced by a platinum–acridine antitumor agent and its effects in NCI-H460 lung cancer cells

Structures of oxaliplatin‐oligonucleotide adducts from DNA

Contact Info

Product

Resources

About