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Comparing the Relative Oxidative DNA Damage Caused by Various Arsenic Species by Quantifying Urinary Levels of 8-Hydroxy-2′-Deoxyguanosine with Isotope-Dilution Liquid Chromatography/Mass Spectrometry

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Abstract

Purpose

To investigate the association between various arsenicals and the potential oxidative stress caused, we examined the urinary levels of 8-hydroxy-2′-deoxyguanosine (8-OH-dGuo), a biomarker of oxidative DNA damage in rats after daily oral administration of arsenic trioxide/arsenite (As2O3), realgar (α-As4S4) and orpiment (As2S3) over 14 days and compared the levels with control rats.

Methods

8-OH-dGuo in urine was quantified with isotope-dilution liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS) after sample cleaning with solid phase extraction (SPE). Urinary arsenic concentrations were measured by graphite furnace atomic absorption spectrometry (GFAAS).

Results

All arsenicals caused elevated urinary 8-OH-dGuo excretion in rats from day 1 after oral administration (p < 0.01 respectively). There were significant correlations between urinary 8-OH-dGuo and urinary arsenic levels (slope = 0.8164, 0.5801, 0.6582; r 2 = 0.5946, 0.7883, 0.8426 for arsenite, realgar and orpiment-treated group respectively, p < 0.001). This illustrates that urinary 8-OH-dGuo level could be a valid biomarker for detecting the extent of arsenic exposure. Arsenite was found to cause significantly higher urinary 8-OH-dGuo levels than both realgar and orpiment (p < 0.01) even after creatinine and dose adjustments.

Conclusions

Arsenite could cause more oxidative DNA damage than both realgar and orpiment and may be more genotoxic.

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Acknowledgements

The study was supported by research grants, R148-000-032-112 and R148-000-097-112 from the National University of Singapore. We thank Dr Xin Liu of the University of Queensland and Dr Haishu Lin of the National University of Singapore for assisting in the animal experimentation.

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Authors and Affiliations

  1. Department of Pharmacy, Faculty of Science National University of Singapore, 18 Science Drive 4, Singapore, 117543, Singapore

    Jin-Zhu Wu & Paul C. Ho

  2. Department of Applied Chemistry, Faculty of Science, Harbin Institute of Technology, Harbin, 150001, China

    Jin-Zhu Wu

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Correspondence to Paul C. Ho.

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Wu, JZ., Ho, P.C. Comparing the Relative Oxidative DNA Damage Caused by Various Arsenic Species by Quantifying Urinary Levels of 8-Hydroxy-2′-Deoxyguanosine with Isotope-Dilution Liquid Chromatography/Mass Spectrometry. Pharm Res 26, 1525–1533 (2009). https://doi.org/10.1007/s11095-009-9865-7

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