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

Abstract

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 (As(2)O(3)), realgar (alpha-As(4)S(4)) and orpiment (As(2)S(3)) over 14 days and compared the levels with control rats. 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). 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. Arsenite could cause more oxidative DNA damage than both realgar and orpiment and may be more genotoxic.