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

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Low 8-oxo-7,8-dihydro-2'-deoxyguanosine levels and influence of genetic background in an Andean population exposed to high levels of arsenic. / Engström, Karin; Vahter, Marie; Lindh, Christian; Teichert, Friederike; Singh, Rajinder; Concha, Gabriela; Nermell, Barbro; Farmer, Peter B; Strömberg, Ulf; Broberg Palmgren, Karin.

I: Mutation Research, Vol. 683, Nr. 1-2, 2010, s. 98-105.

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Engström, Karin ; Vahter, Marie ; Lindh, Christian ; Teichert, Friederike ; Singh, Rajinder ; Concha, Gabriela ; Nermell, Barbro ; Farmer, Peter B ; Strömberg, Ulf ; Broberg Palmgren, Karin. / Low 8-oxo-7,8-dihydro-2'-deoxyguanosine levels and influence of genetic background in an Andean population exposed to high levels of arsenic. I: Mutation Research. 2010 ; Vol. 683, Nr. 1-2. s. 98-105.

RIS

TY - JOUR

T1 - Low 8-oxo-7,8-dihydro-2'-deoxyguanosine levels and influence of genetic background in an Andean population exposed to high levels of arsenic.

AU - Engström, Karin

AU - Vahter, Marie

AU - Lindh, Christian

AU - Teichert, Friederike

AU - Singh, Rajinder

AU - Concha, Gabriela

AU - Nermell, Barbro

AU - Farmer, Peter B

AU - Strömberg, Ulf

AU - Broberg Palmgren, Karin

PY - 2010

Y1 - 2010

N2 - 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 4.7nmol/L (adjusted for specific weight; range 1.6-13, corresponding to 1.7mug/g creatinine, range 0.57-4.8) and of total urinary As metabolites (U-As) 290mug/L (range 94-720; 380mug/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.

AB - 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 4.7nmol/L (adjusted for specific weight; range 1.6-13, corresponding to 1.7mug/g creatinine, range 0.57-4.8) and of total urinary As metabolites (U-As) 290mug/L (range 94-720; 380mug/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.

U2 - 10.1016/j.mrfmmm.2009.10.014

DO - 10.1016/j.mrfmmm.2009.10.014

M3 - Article

VL - 683

SP - 98

EP - 105

JO - Mutation Research

T2 - Mutation Research

JF - Mutation Research

SN - 1873-135X

IS - 1-2

ER -