Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples

Rachel C. Le Pla; Kenneth J. Ritchie; Colin J. Henderson; C. Roland Wolf; Chris F. Harrington; Peter B. Farmer

doi:10.1021/tx700088j

Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples

Rachel C. Le Pla, Kenneth J. Ritchie, Colin J. Henderson, C. Roland Wolf, Chris F. Harrington, Peter B. Farmer

Research output: Contribution to journal › Article › peer-review

27 Citations (Scopus)

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 chromatographyelectrospray ionization tandem mass spectrometry (LCESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GGoxPt and AGoxPt 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.

Original language	English
Pages (from-to)	1177-1182
Number of pages	6
Journal	Chemical Research in Toxicology
Volume	20
Issue number	8
DOIs	https://doi.org/10.1021/tx700088j
Publication status	Published - Aug 2007

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title = "Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples",

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 chromatographyelectrospray ionization tandem mass spectrometry (LCESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GGoxPt and AGoxPt 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.",

author = "{Le Pla}, {Rachel C.} and Ritchie, {Kenneth J.} and Henderson, {Colin J.} and Wolf, {C. Roland} and Harrington, {Chris F.} and Farmer, {Peter B.}",

year = "2007",

month = aug,

doi = "10.1021/tx700088j",

language = "English",

volume = "20",

pages = "1177--1182",

journal = "Chemical Research in Toxicology",

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publisher = "American Chemical Society",

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Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples. / Le Pla, Rachel C.; Ritchie, Kenneth J.; Henderson, Colin J. et al.
In: Chemical Research in Toxicology, Vol. 20, No. 8, 08.2007, p. 1177-1182.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples

AU - Le Pla, Rachel C.

AU - Ritchie, Kenneth J.

AU - Henderson, Colin J.

AU - Wolf, C. Roland

AU - Harrington, Chris F.

AU - Farmer, Peter B.

PY - 2007/8

Y1 - 2007/8

N2 - 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 chromatographyelectrospray ionization tandem mass spectrometry (LCESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GGoxPt and AGoxPt 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.

AB - 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 chromatographyelectrospray ionization tandem mass spectrometry (LCESI-MS/MS) method for measuring GG and AG intrastrand cross-links formed by oxaliplatin. The limits of detection for GGoxPt and AGoxPt 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.

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DO - 10.1021/tx700088j

M3 - Article

SN - 0893-228X

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JO - Chemical Research in Toxicology

JF - Chemical Research in Toxicology

IS - 8

ER -

Development of a liquid Chromatography-Electrospray ionization tandem mass spectrometry method for detecting Oxaliplatin-DNA intrastrand cross-links in biological samples

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