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.
OBJECTIVE
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.


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.
Wu
Jin-Zhu
JZ
Department of Pharmacy, Faculty of Science National University of Singapore, 18 Science Drive 4, Singapore.
Ho
Paul C
PC
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D001152:Arsenicals / Q000008:administration & dosage / Q000009:adverse effects*; D018053:Arsenites / Q000008:administration & dosage / Q000009:adverse effects; D002853:Chromatography, Liquid / Q000379:methods*; D004249:DNA Damage / Q000187:drug effects*; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000652:urine; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D013440:Sulfides / Q000008:administration & dosage / Q000009:adverse effects; D053719:Tandem Mass Spectrometry / Q000379:methods*
D001152:Arsenicals; D018053:Arsenites; D013440:Sulfides; C045816:arsenic trisulfide; C058317:arsenic disulfide; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; C015001:arsenite