Development of a liquid chromatography-electrospray ionization tandem mass spectrometry method for detecting oxaliplatin-DNA intrastrand cross-links in biological samples.

2.50
Hdl Handle:
http://hdl.handle.net/10146/36752
Title:
Development of a liquid chromatography-electrospray ionization tandem mass spectrometry method for detecting oxaliplatin-DNA intrastrand cross-links in biological samples.
Authors:
Le Pla, Rachel C.; Ritchie, Kenneth J.; Henderson, Colin J.; Wolf, C. Roland; Harrington, Chris F.; Farmer, Peter B.
Abstract:
Cellular resistance, both intrinsic and acquired, poses a problem in the effectiveness of platinum-based chemotherapy. The cytotoxic activity of Pt-based chemotherapeutic agents is derived from their ability to react with cellular DNA. Oxaliplatin binds to the N7 position of the purine DNA bases, forming mainly intrastrand cross-links between either two adjacent guanines (GG), an adjacent adenine and guanine (AG), or two guanines separated by an unmodified nucleotide (GNG). We report the development of a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GG-oxPt and AG-oxPt were 23 and 19 adducts per 10 (8) nucleotides, respectively. We compare the formation and persistence of intrastrand cross-links between wild-type and glutathione transferase P null mice (GSTP null) treated with oxaliplatin. No significant difference was observed in the level of intrastrand cross-links formed by oxaliplatin between the mouse strains in liver, kidney, and lung DNA. Adduct levels were greatest in liver and lowest in lung tissue.
Citation:
Chem. Res. Toxicol. 2007, 20 (8):1177-1182
Journal:
Chemical Research in Toxicology
Issue Date:
Aug-2007
URI:
http://hdl.handle.net/10146/36752
DOI:
10.1021/tx700088j
PubMed ID:
17636892
Additional Links:
http://pubs.acs.org/cgi-bin/abstract.cgi/crtoec/2007/20/i08/abs/tx700088j.html
Type:
Article
Language:
en
ISSN:
0893-228X
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorLe Pla, Rachel C.-
dc.contributor.authorRitchie, Kenneth J.-
dc.contributor.authorHenderson, Colin J.-
dc.contributor.authorWolf, C. Roland-
dc.contributor.authorHarrington, Chris F.-
dc.contributor.authorFarmer, Peter B.-
dc.date.accessioned2008-08-28T11:32:02Z-
dc.date.available2008-08-28T11:32:02Z-
dc.date.issued2007-08-
dc.identifier.citationChem. Res. Toxicol. 2007, 20 (8):1177-1182en
dc.identifier.issn0893-228X-
dc.identifier.pmid17636892-
dc.identifier.doi10.1021/tx700088j-
dc.identifier.urihttp://hdl.handle.net/10146/36752-
dc.description.abstractCellular resistance, both intrinsic and acquired, poses a problem in the effectiveness of platinum-based chemotherapy. The cytotoxic activity of Pt-based chemotherapeutic agents is derived from their ability to react with cellular DNA. Oxaliplatin binds to the N7 position of the purine DNA bases, forming mainly intrastrand cross-links between either two adjacent guanines (GG), an adjacent adenine and guanine (AG), or two guanines separated by an unmodified nucleotide (GNG). We report the development of a liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GG-oxPt and AG-oxPt were 23 and 19 adducts per 10 (8) nucleotides, respectively. We compare the formation and persistence of intrastrand cross-links between wild-type and glutathione transferase P null mice (GSTP null) treated with oxaliplatin. No significant difference was observed in the level of intrastrand cross-links formed by oxaliplatin between the mouse strains in liver, kidney, and lung DNA. Adduct levels were greatest in liver and lowest in lung tissue.en
dc.language.isoenen
dc.relation.urlhttp://pubs.acs.org/cgi-bin/abstract.cgi/crtoec/2007/20/i08/abs/tx700088j.htmlen
dc.subject.meshAnimals-
dc.subject.meshAntineoplastic Agents-
dc.subject.meshChromatography, Liquid-
dc.subject.meshCisplatin-
dc.subject.meshCross-Linking Reagents-
dc.subject.meshDNA-
dc.subject.meshDNA Adducts-
dc.subject.meshMice-
dc.subject.meshMice, Knockout-
dc.subject.meshOrganoplatinum Compounds-
dc.subject.meshSpectrometry, Mass, Electrospray Ionization-
dc.subject.meshTandem Mass Spectrometry-
dc.subject.meshTissue Distribution-
dc.titleDevelopment of a liquid chromatography-electrospray ionization tandem mass spectrometry method for detecting oxaliplatin-DNA intrastrand cross-links in biological samples.en
dc.typeArticleen
dc.identifier.journalChemical Research in Toxicologyen
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