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, Karin

doi:10.1016/j.mrfmmm.2009.10.014

Cited by 27 publications

(27 citation statements)

References 46 publications

(61 reference statements)

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“…Our findings, as well as the inconsistent findings from other population-based studies examining associations between As exposure and blood markers of oxidative damage (Burgess et al 2007; Engström et al 2010a, 2010b; Pi et al 2002), raise the possibility that, despite reductions in GSH, As may not induce substantial, sustained oxidative stress that is measurable in blood using these biomarkers at environmentally relevant As exposures. We cannot determine from this study what the functional effects of the observed reduction in blood GSH might be; however, alterations in GSH have been linked to the development and/or progression of numerous diseases (Ballatori et al 2009).…”

Section: Discussioncontrasting

confidence: 62%

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Hall¹,

Niedzwiecki

Liu

et al. 2013

Environ Health Perspect

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Background: In vitro and rodent studies have shown that arsenic (As) exposure can deplete glutathione (GSH) and induce oxidative stress. GSH is the primary intracellular antioxidant; it donates an electron to reactive oxygen species, thus producing glutathione disulfide (GSSG). Cysteine (Cys) and cystine (CySS) are the predominant thiol/disulfide redox couple found in human plasma. Arsenic, GSH, and Cys are linked in several ways: a) GSH is synthesized via the transsulfuration pathway, and Cys is the rate-limiting substrate; b) intermediates of the methionine cycle regulate both the transsulfuration pathway and As methylation; c) GSH serves as the electron donor for reduction of arsenate to arsenite; and d) As has a high affinity for sulfhydryl groups and therefore binds to GSH and Cys.Objectives: We tested the hypothesis that As exposure is associated with decreases in GSH and Cys and increases in GSSG and CySS (i.e., a more oxidized environment).Methods: For this cross-sectional study, the Folate and Oxidative Stress Study, we recruited a total of 378 participants from each of five water As concentration categories: < 10 (n = 76), 10–100 (n = 104), 101–200 (n = 86), 201–300 (n = 67), and > 300 µg/L (n = 45). Concentrations of GSH, GSSG, Cys, and CySS were measured using HPLC.Results: An interquartile range (IQR) increase in water As was negatively associated with blood GSH (mean change, –25.4 µmol/L; 95% CI: –45.3, –5.31) and plasma CySS (mean change, –3.00 µmol/L; 95% CI: –4.61, –1.40). We observed similar associations with urine and blood As. There were no significant associations between As exposure and blood GSSG or plasma Cys.Conclusions: The observed associations are consistent with the hypothesis that As may influence concentrations of GSH and other nonprotein sulfhydryls through binding and irreversible loss in bile and/or possibly in urine.Citation: Hall MN, Niedzwiecki M, Liu X, Harper KN, Alam S, Slavkovich V, Ilievski V, Levy D, Siddique AB, Parvez F, Mey JL, van Geen A, Graziano J, Gamble MV. 2013. Chronic arsenic exposure and blood glutathione and glutathione disulfide concentrations in Bangladeshi adults. Environ Health Perspect 121:1068–1074; http://dx.doi.org/10.1289/ehp.1205727

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Section: Discussioncontrasting

confidence: 62%

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Hall¹,

Niedzwiecki

Liu

et al. 2013

Environ Health Perspect

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“…In Calchaqu ıes (IA), exposure to moderate hypoxia and milder climate (Bianchi and Cravero 2010) may exert a weaker pressure on bone growth than in Collas (HA). Their reduction in distal limb lengths, however, may not be adaptive per se but may indicate the prioritization of oxygen use throughout the organism (Pomeroy et al 2012), alongside other physiological strategies such as the increased hematocrit, which although was not measured in our sample, is well documented among Andeans (Frisancho 1975;Engstr€ om et al 2010). While tibia and forearm length reduction was only observed in highland Collas, lung volume was increased in Collas and Calchaqu ıes (IA) alike (Table 3).…”

Section: Discussionmentioning

confidence: 80%

Genetic and Phenotypic Differentiation of an Andean Intermediate Altitude Population

et al. 2016

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Highland populations living permanently under hypobaric hypoxia have been subject of extensive research because of the relevance of their physiological adaptations for the understanding of human health and disease. In this context, what is considered high altitude is a matter of interpretation and while the adaptive processes at high altitude (above 3000 m) are well documented, the effects of moderate altitude (below 3000 m) on the phenotype are less well established. In this study, we compare physiological and anthropometric characteristics as well as genetic variations in two Andean populations: the Calchaqu ıes (2300 m) and neighboring Collas (3500 m). We compare their phenotype and genotype to the sea-level Wich ı population. We measured physiological (heart rate, oxygen saturation, respiration rate, and lung function) as well as anthropometric traits (height, sitting height, weight, forearm, and tibia length). We conducted genome-wide genotyping on a subset of the sample (n = 74) and performed various scans for positive selection. At the phenotypic level (n = 179), increased lung capacity stood out in both Andean groups, whereas a growth reduction in distal limbs was only observed at high altitude. At the genome level, Calchaqu ıes revealed strong signals around PRKG1, suggesting that the nitric oxide pathway may be a target of selection. PRKG1 was highlighted by one of four selection tests among the top five genes using the population branch statistic. Selection tests results of Collas were reported previously. Overall, our study shows that some phenotypic and genetic differentiation occurs at intermediate altitude in response to moderate lifelong selection pressures.

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“…Exposure during these times has also been implicated in adverse reproductive outcomes in mothers and impaired cognitive development in children (Hopenhayn-Rich et al, 2000; Hopenhayn et al, 2003a). Recent studies have examined the possible mechanisms of toxicity that bring about these adverse health outcomes, including genotoxicity, oxidative stress, and impaired DNA repair (Dulout et al, 1996; Engstrom et al, 2007; Engstrom et al, 2009; Engstrom et al, 2010). …”

Section: Introductionmentioning

confidence: 99%

Arsenic exposure in Latin America: Biomarkers, risk assessments and related health effects

McClintock

Chen

Bundschuh

et al. 2012

Science of The Total Environment

155

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In Latin America, several regions have a long history of widespread arsenic (As) contamination from both natural and anthropological sources. Yet, relatively little is known about the extent of As exposure from drinking water and its related health consequences in these countries. It has been estimated that at least 4.5 million people in Latin America are chronically exposed to high levels of As (>50µg/L), some to as high as 2000 µg/L - 200 times higher than the World Health Organization (WHO) provisional standard for drinking water. We conducted a systematic review of 82 peer reviewed papers and reports to fully explore the current understanding of As exposure and its health effects, as well as the influence of genetic factors that modulate those effects in the populations of Latin America. Despite some methodological limitations, these studies suggested important links between high levels of chronic As exposure and elevated risks of numerous adverse health outcomes in Latin America - including internal and external cancers, reproductive outcomes, and childhood cognitive function. Several studies demonstrated genetic polymorphisms that influence susceptibility to these and other disease states through their modulation of As metabolism, with As methyltransferase (AS3MT), glutathione S-transferase (GST), and genes of one-carbon metabolism being specifically implicated. While the full extent and nature of the health burden are yet to be known in Latin America, these studies have significantly enriched knowledge of As toxicity and led to subsequent research. Targeted future studies will not only yield a better understanding of the public health impact of As in Latin America populations, but also allow for effective and timely mitigation efforts.

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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

Cited by 27 publications

References 46 publications

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Chronic Arsenic Exposure and Blood Glutathione and Glutathione Disulfide Concentrations in Bangladeshi Adults

Genetic and Phenotypic Differentiation of an Andean Intermediate Altitude Population

Arsenic exposure in Latin America: Biomarkers, risk assessments and related health effects

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