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; r2=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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