Determination of 8-oxo-2'-deoxyguanosine and creatinine in murine and human urine by liquid chromatography/tandem mass spectrometry: application to chemoprevention studies.

Abstract

Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) represents a non-invasive biomarker for oxidative stress and may be useful for monitoring chemotherapeutic and chemopreventive interventions associated with cancer-related alterations in oxidative stress. We describe the development and validation of two separate liquid chromatography/tandem mass spectrometry (LC/MS/MS) selected reaction monitoring (SRM) methods for the determination of 8-oxodG and creatinine in both murine and human urine using stable isotope labelled internal standards. Levels of 8-oxodG were normalised to creatinine. The LC/MS/MS methods were applied to two chemoprevention studies utilising tea polyphenols in humans and TRAMP (TRansgenic Adenocarcinoma of the Mouse Prostate) mice. Patients with benign prostatic hyperplasia received 1 g/day of green tea polyphenols (GTP), 1 g/day of black tea theaflavins (BTT) or no treatment for 4 weeks. TRAMP mice received GTP (0.05% in drinking water) for 4 or 25 weeks. Prostate pathology in TRAMP mice was not affected by GTP. Levels of 8-oxodG were not altered by tea polyphenols in either mice or humans. In TRAMP mice, urinary 8-oxodG levels were elevated with increasing age (p < 0.0001) but not changed by the presence of prostate tumours. In conclusion, the LC/MS/MS SRM methods described here are ideally suited for the accurate determination of 8-oxodG and creatinine in urine samples from both clinical and pre-clinical studies.

• Authors: Friederike Teichert, Richard D Verschoyle, Peter Greaves, James F Thorpe, J Kilian Mellon, William P Steward, Peter B Farmer, Andreas J Gescher, Rajinder Singh
• Journal: Rapid communications in mass spectrometry : RCM (Rapid Commun Mass Spectrom) Vol. 23 Issue 2 Pg. 258-66 (Jan 2009) ISSN: 0951-4198 [Print] England
• PMID: 19072863 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2008 John Wiley & Sons, Ltd.

Chemical References

• Antineoplastic Agents
• Plant Extracts
• Tea
• 8-Hydroxy-2'-Deoxyguanosine
• Creatinine
• Deoxyguanosine

Topics

• 8-Hydroxy-2'-Deoxyguanosine
• Adenocarcinoma (urine)
• Animals
• Antineoplastic Agents (administration & dosage, pharmacokinetics)
• Cell Line, Tumor
• Chromatography, High Pressure Liquid (methods)
• Creatinine (urine)
• Deoxyguanosine (analogs & derivatives, urine)
• Humans
• Male
• Mice
• Mice, Inbred C57BL
• Plant Extracts (administration & dosage, pharmacokinetics)
• Prostatic Neoplasms (urine)
• Reproducibility of Results
• Sensitivity and Specificity
• Spectrometry, Mass, Electrospray Ionization (methods)
• Tea (chemistry)
• Urinalysis (methods)