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Mutat Res. 2010 Jan 5;683(1-2):98-105. doi: 10.1016/j.mrfmmm.2009.10.014.

Low 8-oxo-7,8-dihydro-2'-deoxyguanosine levels and influence of genetic background in an Andean population exposed to high levels of arsenic.

Author information

1
Department of Laboratory Medicine, Lund University Hospital, Lund, Sweden. Karin.engstrom@med.lu.se

Abstract

BACKGROUND:

Arsenic (As) causes oxidative stress through generation of reactive oxygen species. 8-Oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a sensitive marker of oxidative DNA damage, has been associated with As exposure in some studies, but not in others, possibly due to population-specific genetic factors.

OBJECTIVES:

To evaluate the association between As and 8-oxodG in urine in a population with a low urinary monomethylated As (%MMA) and high dimethylated As (%DMA), as well as the genetic impact on (a) 8-oxodG concentrations and (b) the association between As and 8-oxodG.

MATERIALS AND METHODS:

Women (N=108) in the Argentinean Andes were interviewed and urine was analyzed for arsenic metabolites (ICPMS) and 8-oxodG (LC-MS/MS). Twenty-seven polymorphisms in genes related to oxidative stress and one in As(+III)methyltransferase (AS3MT) were studied.

RESULTS:

Median concentration of 8-oxodG was 4.7 nmol/L (adjusted for specific weight; range 1.6-13, corresponding to 1.7 microg/g creatinine, range 0.57-4.8) and of total urinary As metabolites (U-As) 290 microg/L (range 94-720; 380 microg/g creatinine, range 140-1100). Concentrations of 8-oxodG were positively associated with %MMA (strongest association, p=0.013), and weakly associated with U-As (positively) and %DMA (negatively). These associations were strengthened when taking ethnicity into account, possibly reflecting genetic differences in As metabolism and genes regulating oxidative stress and DNA maintenance. A genetic influence on 8-oxodG concentrations was seen for polymorphisms in apurinic/apyrimidinic endonuclease 1 (APEX1), DNA-methyltransferases 1 and 3b (DNMT1, DNMT3B), thioredoxin reductase 1 (TXNRD1) and 2 (TXNRD2) and glutaredoxin (GLRX).

CONCLUSION:

Despite high As exposure, the concentrations of 8-oxodG in this population were low compared with other As-exposed populations studied. The strongest association was found for %MMA, stressing that some inconsistencies between As and 8-oxodG partly depend on population variations in As metabolism. We found evidence of genetic impact on 8-oxodG concentrations.

PMID:
19896490
DOI:
10.1016/j.mrfmmm.2009.10.014
[Indexed for MEDLINE]

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