Chronic inflammation in mice exposed to the long-term un-entrainable light–dark cycles

Shift work is indispensable in our modern society; therefore, measures for maintaining the health of shift workers are urgently required. In this prospective study observing the effects of different types of scheduled light–dark shift conditions in wild-type mice, we reared mice for 630 days under two chronic jet lag conditions with distinct programs of light and darkness: an 8-h phase delay every 7 days (delay, n = 14) or an 8-h phase advance every 4 days (advance, n = 34). “Delay” represents a mild condition in which mice are entrained, whereas “Advance” represents a condition of circadian rhythm disorder in which mice are not entrained. Our results showed that the 26.5% (9/34) mice reared under the “Advance” shift condition died or were sacrificed by humane endpoint throughout the experiment, whereas the first death under “Delay” condition occurred on day 611. The mortality rate of the mice reared under “Advance” condition was higher than the mice under “Delay” condition [HR (95% CI) 4.26 (0.54–33.6)]. In “Advance” mice of shorter lifespan, which showed splenomegaly and increased myeloid cells in bone marrow, which indicates that chronic inflammation existed in those mice. Although this study is still preliminary, these findings suggest that prolonged severe circadian rhythm disorder may result in the induction of chronic inflammation and tend to result in a shorter lifespan. Further studies are needed to understand why and how circadian rhythm disorder increases the risk of various dysfunction of physiology and diseases.

     

Impacts of drought on leaf respiration in darkness and light in Eucalyptus saligna exposed to industrial-age atmospheric CO₂ and growth temperature

Our study assessed the impact of a wide range of industrial-age climate scenarios on leaf respiration (R) in Eucalyptus saligna. Well-watered or sustained drought-treated plants were grown in glasshouses differing in atmospheric CO? concentration ([CO?]) (280, 400 and 640 μl l?1) and temperature (26 and 30°C). Rates of R in darkness (R(dark) ) and light (R(light) ), photosynthesis (A) and related leaf traits (mass : area relationships, and nitrogen, phosphorus, starch and sugar concentrations) were measured. Light inhibited R in all cases (R(light) < R(dark) ) (well-watered: 40%; drought-treated: 73%). Growth [CO?] and temperature had little impact on area-based rates of R(dark) or R(light) , with R(light) exhibiting minimal thermal acclimation. By contrast, sustained drought resulted in reduced R(dark), R(light) and A, with the inhibitory effect of drought on A and R(light) (c. 50-70%) greater than that on R(dark) (c. 15%). Drought effects were fully reversible after watering. Variability in R(light) appeared to be dependent on the underlying rate of R(dark) and associated Rubisco activity. Collectively, our data suggest that there is an asynchronous response of leaf carbon metabolism to drought, and a tighter coupling between R(light) and A than between R(dark) and A, under both past and future climate scenarios. These findings have important implications for ecosystem/global models seeking to predict carbon cycling.     

Photochemical metabolism and fruit quality of Ubá mango tree exposed to combined light and heat stress in the field

Several experiments have highlighted the complexity of stress interactions, in field conditions, involved in plant response. However, these impacts on the mechanisms involved in plant photosynthetic response remains understudied. The aim of this work was to compare the photosynthetic efficiencies and fruit quality of mango tree (Mangifera indica L.) cv. Ubá harvested from plants cultivated on the east and west sides of a commercial orchard, according to the position of plants in relation to sunrise. Chlorophyll a fluorescence, was analyzed in leaves in four different periods: fruit growth phase, fruit ripening phase, post-harvest period and after plant pruning. Photoinhibitory damage was detected by the trapped energy flux and transported electron flux per reaction center during the fruit ripening phase, and by specific energy fluxes and yield quantum efficiency after plant pruning. Although high radiation caused photoinhibition on leaves from plants cultivated on the west side of the orchard, it provided sweeter fruits. In contrast to our initial hypothesis, it was verified that plants cultivated on the west side of the orchard presented better photochemical performance in periods with the greatest requirements of photoassimilates. In addition, plants demonstrated different abilities to deal with changes on photosynthetic active radiation and high temperature. This information suggests that the phenotypic plasticity of the Ubá mango cultivar is considerable, which can be exploited to be used in regions with great relief variations and the combination of increased irradiance and high temperature.     

Spatial and temporal variation in the vegetation of dune slacks in relation to the ground water régime

Summary The aim of the study presented here is to determine the relation between the vegetation and the ground water régime in the dune slacks on the island of Voorne. A distinction is made between the spatial and the temporal variation in the vegetation. On the basis of data from a transect the relation between the spatial variation and the water-table is determined. With respect to the temporal variation data recorded on permanent plots were used. Both the variation in space and that in time proved to be related to differences in the ground water régime. The supposition is put forward that the amount of variation in time depends on the height of site relative to the water-table.Contribution to the Symposium of the Working Group on Succession Research on Permanent Plots held at Yerseke, the Netherlands, October 1975.Nomenclature of phanerogams follows Heukels & van Ooststroom 1975, Flora van Nederland, 18e druk Wolters-Noordhoff, Groningen; that of bryophytes Margadant 1959, Mossentabel, 3e druk, Amsterdam.The author is very much indebted to Mr. P.A. Bakker, Society for the Preservation of Nature reserves in the Netherlands, for the use of the 1966 relevé of site 46, and to Mr. W. Smant for his assistance in field work and the preparation of the data.     

Rabies in urban foxes (Vulpes vulpes) in Britain: the use of a spatial stochastic simulation model to examine the pattern of spread and evaluate the efficacy of different control régimes.

The threat of rabies being reintroduced into Britain is probably greater now than at any time over the last 60 years. This threat is reviewed with particular regard to the problems that would be posed should rabies be introduced to the high-density fox populations found in many cities in southern England. Computer models can provide a valuable means of understanding the pattern of rabies spread in fox populations and the likely problems of control, so the construction of previous rabies models was reviewed. None were found to be suitable for analysing the particular problems posed by high-density, spatially heterogeneous, urban fox populations. Therefore, a new spatial stochastic simulation model was produced, based on demographic and other data collected during a long-term study on the urban fox population in Bristol, and fox density data collected from a number of cities in southern England. The simulation model was used to analyse the effects of spatial heterogeneity in the fox population on the pattern of rabies spread. Simulations were then used to evaluate the effects of: (i) varying levels of fox control; (ii) changing the size of the control zone; (iii) the onset of the rabies epizooty at different times of the year: and (iv) delay before the commencement of control on the chances of containing the disease. These simulations were run for four cities (Bournemouth and Poole, Bristol, Leicester and the West Midlands conurbation) with different mean fox population densities. It was found that the variance in the monthly velocity of the rabies front was greater for heterogeneous fox populations. In cities with high fox densities, low or moderate levels of control were unsuccessful in containing the disease, but these urban areas had the highest rates of success with the highest levels of control. A three-month delay in the commencement of a rabies control campaign on average reduced the chance of successfully controlling the disease by 10-20%, although this was higher in lower-density fox populations. Rabies outbreaks in the dispersal period were on average 10% less likely to be contained. Increasing the size of the control zone increased the chances of successfully containing the disease, although this effect was density dependent, so the effect was less in low-density fox populations. These results are discussed in relation to the current rabies contingency plans for British urban areas.     

Determination and characterization of cysteine, glutathione and phytochelatins (PC₂₋₆) in Lolium perenne L. exposed to Cd stress under ambient and elevated carbon dioxide using HPLC with fluorescence detection

Metal-binding thiols, involved in detoxification mechanisms in plant and other organism under heavy metal stress, are receiving more and more attentions, and various methods have been developed to determine related thiols such as cysteine (Cys), glutathione (GSH) and phytochelatins (PCs). In present study, an HPLC method was established for simultaneous determination of Cys GSH and PC(2-6) after treatment with disulfide reductant of tris (2-carboxyethyl) phosphine hydrochloride (TCEP) and thiolyte reagent of monobromobimane (mBBr). The separation of thiol derivatives was performed on an Agilent Zorbax Eclipse XDB-C18 column (4.6 mm × 30 mm, 1.8 μm) with a linear gradient elution of 0.1% (v/v) trifluoroacetic acid (TFA)-acetonitrile (ACN) at 0.8 mL min(-1). The temperature of the column was maintained at 25°C. The excitation and emission wavelengths were set at 380 and 470 nm, respectively. The thiol derivatives were well separated in 19 min, and the total analysis time was 30 min. The established method was proved selective, specific and reproducible, and could be applicable to determine Cys, GSH and PC(2-6) and to evaluate their roles in detoxification mechanisms in Cd-treated Lolium perenne L. under ambient and elevated carbon dioxide (CO(2)). It was found that the total SH contents and proportions of thiols in roots and shoots were dependent on Cd concentration, whereas the total SH contents decreased and the proportions of thiols altered without significance at elevated CO(2) level.     

Susceptibility to oxidative stress in Adélie and emperor penguin

The antioxidant defences in aerobic organisms represent the detoxification pathway against toxicity of reactive oxygen species (ROS). These highly reactive molecules are normally produced during the 4-electrons reduction of molecular oxygen to water coupled with oxidative phosphorylation, and during the activity of several enzymatic systems which produce ROS as intermediates. However, the endogenous generation of oxyradicals may be influenced by different environmental and biological factors, and the basal efficiency of antioxidant systems generally reflects the normal prooxidant pressure to which organisms are exposed. If the antioxidant capacity is exceeded (i.e. as a consequence of enhanced intracellular formation of ROS), a pathological condition, generally termed oxidative stress, may arise. In this preliminary work, susceptibility to oxidative stress has been compared in plasma of Adélie penguin (Pygoscelis adeliae), emperor penguin (Aptenodytes forsteri), south polar skua (Catharacta maccormicki) and snow petrel (Pagodroma nivea). Within the framework of the Italian Research Program in Antarctica, blood samples were collected during the austral summer 1998-1999 and the Total Oxyradical Scavenging Capacity (TOSC) analysed. The TOSC assay, measuring the capability of biological samples to neutralise different oxyradicals, has been recently standardised to provide a quantifiable value of biological resistance to toxicity of ROS. Penguins exhibited higher scavenging capacity towards peroxyl radicals than south polar skua and snow petrel. The greater resistance to toxicity of oxyradicals might suggest that penguins are naturally exposed to a higher basal prooxidant pressure in comparison to other analysed Antarctic birds.     

Localization of hydrogen peroxide in pumpkin (Cucurbita ficifolia bouché) seedlings exposed to high-dose gamma ray

Hydrogen peroxide (H₂O₂) was detected cytochemically, via transmission electron microscopy (TEM), in pumpkin tissues exposed to high-dose gamma ray. Its reaction with cerium chloride produced electron-dense precipitates of cerium perhydroxides. Their patterns of deposition in the tissues of both control plants and those irradiated with gamma ray (PIG) were typically found in the plasma membranes and cell walls. However, gamma irradiation remarkably increased the intensities of cerium perhydroxide deposits (CPDs) in the plasma membranes and cell walls for all tissue types, but especially the leaves. The only exception was for vessels in the cotyledons. After gamma irradiation, the (H₂O₂) content in all tissues was higher than in the control samples, except for the cotyledons of PIG, where the (H₂O₂) content was lower than for all others. The increased appearance of CPDs may have been due to the enhancement of (H₂O₂) accumulation by gamma radiation. This accumulation also varied according to the cell or tissue type examined.     

Relation Between Personality and Ventilatory Response to Carbon Dioxide in Normal Subjects: A Role in Asthma?

Ventilatory response to carbon dioxide, as an index of respiratory centre sensitivity, was measured in 50 normal subjects. Their personality was documented in terms of extraversion and neuroticism scores by the Eysenck Personality Inventory. A significant correlation was found between extraversion score and ventilatory response to carbon dioxide in women (P < 0·005) but not in men. No correlation was found between ventilatory responsiveness and neuroticism score in either sex. It is suggested that the degree of extraversion may play some part in determining the level of ventilation adopted, and hence of arterial carbon dioxide tension, if and when women develop lung disease such as asthma.     

Gammaproteobacterial Diversity and Carbon Utilization in Response to Salinity in the Lakes on the Qinghai–Tibetan Plateau

The Gammaproteobacteria are widely and abundantly distributed in various environments, and they play important roles in the geochemical cycles of biogenic elements (e.g., C, N and S) in the ecosystems. Previous studies showed that Gammaproteobacteria dominate in saline and hypersaline lakes. However, little is known on how salinity influences gammaproteobacterial community composition and their ecological functions (i.e., organic carbon degradation). In this study, we investigated the gammaproteobacterial diversity and carbon utilization and their response to salinity in six saline/hypersaline lakes and one freshwater lake on the Qinghai–Tibetan Plateau (QTP). The results indicated that the gammaproteobacterial community composition was mainly influenced by the salinity of the studied QTP lakes. Salinity was also a key environmental factor influencing the carbon utilization ability of Gammaproteobacteria: within one genus (e.g., Halomonas, Pseudoalteromonas, Vibrio) the strains retrieved from low-salinity environments had stronger carbon utilization ability than their counterparts from high-salinity environments; within one genus, the strains isolated from lakes with different salinity shared similar carbon utilization preference, indicating that species belonging to the same genus may execute similar ecological functions in the environments regardless of salinity.     

ROS and NF-κB are involved in upregulation of IL-8 in A549 cells exposed to multi-walled carbon nanotubes

Carbon nanotubes (CNTs) have potential applications in biosensors, tissue engineering, and biomedical devices because of their unique physico-chemical, electronic and mechanical properties. However, there is limited literature data available concerning the biological properties and toxicity of CNTs. This study aimed to assess the toxicity exhibited by multi-walled CNTs (MWCNTs) and to elucidate possible molecular mechanisms underlying the biological effects of MWCNTs in A549 cells. Exposing A549 cells to MWCNTs led to cell death, changes in cell size and complexity, reactive oxygen species (ROS) production, interleukin-8 (IL-8) gene expression and nuclear factor (NF)-κB activation. Treatment of A549 cells with antioxidants prior to adding MWCNTs decreased ROS production and abrogated expression of IL-8 mRNA. Pretreatment of A549 cells with NF-κB inhibitors suppressed MWCNTs-induced IL-8 mRNA expression. These results indicate that MWCNTs are able to induce expression of IL-8 in A549 cells, at least in part, mediated by oxidative stress and NF-κB activation.     

Is there a relationship between early genotoxicity and life-history traits in Vicia faba exposed to cadmium-spiked soils?

The Vicia faba-micronucleus test is usually performed to assess the genotoxic potential of pure substances, effluents or water extracts from soil. It is also a relevant, early biological tool to detect mutagenic substances in crude soils. Nevertheless, the physiological meaning of such DNA damage for the plant in the long term remains to be elucidated. To know more about this, two experiments were carried out with the plant model V. faba. In a preliminary short-term experiment, seeds were exposed for five days to a soil spiked with different concentrations of CdCl(2) in order to identify the concentration inducing the highest number of micronuclei without affecting plant growth. Thereafter, a long-term experiment was performed in the soil spiked with such a concentration (i.e. 510μmol CdCl(2) per kg dry soil), in which V. faba seeds were directly sowed and allowed to grow during 151 days. As a result, Cd-spiked soil did not affect seed-emergence time nor the growth-rate of the plants for the first two months. The first signs of toxicity appeared after the 70th day of exposure. Interestingly, exposed plants produced their first flower earlier and had a longer flowering period than did control ones. Nevertheless, total flower production was less abundant in exposed plants than in control plants. Moreover, fruits appeared in control plants whereas no fruit was formed in exposed plants. At last, exposed plants showed a reduced life time. Our results suggest that the micronucleus assay can provide a predictive biomarker of long-term deleterious effects in plants.     

Behavior and food consumption pattern of the population exposed in 1949�C1962 to fallout from Semipalatinsk nuclear test site in Kazakhstan

The relationship between radiation exposure from nuclear weapons testing fallout and thyroid disease in a group of 2,994 subjects has been the subject of study by the US National Cancer Institute. In that study, radiation doses to the thyroid were estimated for residents of villages in Kazakhstan possibly exposed to deposition of radioactive fallout from nuclear testing conducted by the Soviet Union at the Semipalatinsk Nuclear Test Site in Kazakhstan between 1949 and 1962. The study subjects included individuals of both Kazakh and Russian origin who were exposed during childhood and adolescence. An initial dose reconstruction used for the risk analysis of Land et al. (Radiat Res 169:373?C383, 2008) was based on individual information collected from basic questionnaires administered to the study population in 1998. However, because data on several key questions for accurately estimating doses were not obtained from the 1998 questionnaires, it was decided to conduct a second data collection campaign in 2007. Due to the many years elapsed since exposure, a well-developed strategy was necessary to encourage accurate memory recall. In our recent study, a focus group interview data collection methodology was used to collect historical behavioral and food consumption data. The data collection in 2007 involved interviews conducted within four-eight-person focus groups (three groups of women and one group of men) in each of four exposed villages where thyroid disease screening was conducted in 1998. Population-based data on relevant childhood behaviors including time spent in- and outdoors and consumption rates of milk and other dairy products were collected from women??s groups. The data were collected for five age groups of children and adolescents ranging from less than 1?year of age to 21?years of age. Dairy products considered included fresh milk and other products from cows, goats, mares, and sheep. Men??s focus group interviews pertained to construction materials of houses and schools, and animal grazing patterns and feeding practices. The response data collected are useful for improving estimates of thyroid radiation dose estimates for the subjects of an ongoing epidemiological study.     

Loss of Hydrogen from Carbon 5 of d-Glucose during Conversion of d-[5-H,6-C]Glucose to l-Ascorbic Acid in Pelargonium crispum (L.) L'Hér

Conversion of d-[5-³H,6-¹⁴C]glucose to l-ascorbic acid in detached apices of Pelargonium crispum (L.) L'Hér cv Prince Rupert (lemon geranium) was accompanied by complete loss of tritium in the product. Chemical degradation of d-glucose which was recovered from the labeled apices yielded d-glyceric acid (corresponding to carbons 4, 5, and 6 of glucose) with a ³H:¹⁴C ratio of 4 to be compared with 9, the ratio in d-[5-³H,6-¹⁴C]glucose initially. Conversion of d-[6-³H,6-¹⁴C]glucose in the same tissue was accompanied by retention of tritium in l-ascorbic acid with a ³H:¹⁴C ratio comparable to that of compounds from the hexose pool. Results indicate that during l-ascorbic acid biosynthesis from glucose in Pelargonium crispum hydrogen at carbon 5 undergoes exchange with the medium, suggesting an epimerization at this carbon atom.     

Carbon and water relations of Salix monticola in response to winter browsing and changes in surface water hydrology: an isotopic study using δ13C and δ18O

To ascertain whether browsing or hydrologic conditions influence the physiological performance of Salix and whether Salix and graminoids (Carex) use and possibly compete for similar water resources, we quantified the in situ seasonal patterns of plant water and carbon relations over three growing seasons. Our studies were designed to address the physiological factors which may be responsible for poor woody plant regeneration in montane riparian habitats of Rocky Mountain National Park, Colo. As these systems act to insure the delivery of fresh water to downstream users, the maintenance of their integrity is critical. We quantified plant water potentials, instantaneous rates of carbon fixation, leaf carbon isotope discrimination (Δ), leaf nitrogen content and water sources using stable isotopes of water (δ¹⁸O). The carbon and water relations of Salix were significantly affected by winter browsing by elk and in some cases by landscape position with regard to proximity to active streams. Winter browsing of Salix by elk significantly increased summer plant water potentials and integrative measures of gas exchange (Δ), though browsing did not consistently affect instantaneous rates of photosynthesis, leaf nitrogen or the sources of water used by Salix. No effect of experimental manipulations of surface water conditions on Salix physiology was observed, likely due to the mesic nature of our study period. Using a two-member linear mixing model, from δ¹⁸O values we calculated that Salix appears to rely on streams for approximately 80% of its water. In contrast, the graminoid Carex derives almost 50% of its water from rainfall, indicating divergent water source use by these two life forms. Based on these findings, winter browsing by elk improved Salix water balance possibly by altering the shoot to root ratio which in turn leads to higher water potentials and higher degrees of season-long gas exchange, while experimental damming had in general no effect on the physiological performance of Salix plants. In addition, as the water sources of Salix and Carex were significantly different, competition for water may not influence the growth, development, and regeneration of Salix. Thus, under the conditions of our study, herbivory had a positive effect on the physiological performance of Salix, but it is still unclear whether these changes in physiology transcend into improved Salix regeneration and survivorship. However, under drier environmental conditions such as lower snowpacks and lower stream flows, the browsing resistance of Salix and ecosystem regeneration may be greatly hindered because the reliance of Salix on stream water makes it vulnerable to changes in surface water and hydrological conditions. Received: 1 July 1998 / Accepted: 23 December 1998     

Immunolabeling of grapevine flavescence dorée MLO in salivary glands of Euscelidius variegatus: a light and electron microscopy study

Flavescence dorée (FD), a grapevine yellows disease, is caused by a mycoplasma-like organism (MLO). A colloidal gold indirect immunolabeling technique identified MLO in salivary glands of a vector leafhopper, Euscelidius variegatus. After aldehyde fixation, tissue samples were prepared by cryoultramicrotomy or embedding in acrylic resins. Double fixation with aldehydes and osmium retroxide, followed by embedding in epon, was also performed. Thin or semi-thin serial sections were treated with polyclonal anti-FD-MLO rabbit antibodies, then with gold-conjugated anti-rabbit IgG. Labeling was revealed using the silver enhancement technique for light microscopy. MLO in frozen thin sections of glands were efficiently labeled. Optimal results were obtained with 4% paraformaldehyde-0.1% glutaraldehyde fixation and low-temperature embedding in LR White resin. Both scattered MLO and unusual dense forms of MLO were easily detected with the electron-dense gold probe. This method distinguished MLO from other membrane-limited bodies and provided a good tool for studying infection in large regions of FD-infected tissues by light microscopy.     

Enhanced Wnt/β-catenin signalling during tooth morphogenesis impedes cell differentiation and leads to alterations in the structure and mineralisation of the adult tooth

BACKGROUND INFORMATION: Previous studies have indicated that over-activation of the wingless interaction site (Wnt)/β-catenin signalling pathway has important implications for tooth development, at the level of cell differentiation and morphology, as well as for the production of supernumerary teeth. Here, we provide evidence for a crucial role of this signalling pathway during the stage of tooth morphogenesis. We have developed an in vitro model consisting of 14.5-day-old mouse embryo first molars, in which the Wnt pathway is overactivated by the glycogen synthase kinase-3 inhibitor 6-bromoindirubin-3'-oxime (BIO; 20 μM). RESULTS: We found that over-activation of the Wnt/β-catenin pathway delayed the differentiation and growth of the inner dental epithelium. In addition, in contrast to controls in which Nestin protein expression was restricted to differentiated odontoblasts, in BIO-treated molars, Nestin expression spread through sub-odontoblastic cellular layers. This alteration appears to be related to: (i) the over-expression of Bmp4 in the same region, (ii) the delay in odontoblast precursor cell differentiation and (iii) increased proliferation of mesenchymal cells. Furthermore, treatments longer than 6 days induced the malformation of typical dental structures and led to a total lack of cell differentiation. Finally, over-activation of the Wnt route during odontogenesis resulted in adult teeth which presented altered size, morphology and mineralisation. CONCLUSIONS: Our results indicate that Wnt/β-catenin over-activation during tooth morphogenesis is sufficient to cause dramatic alterations in the adult tooth, by delaying cellular differentiation and stimulating proliferation of the dental mesenchyme of developing teeth.     

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

BackgroundArsenic (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.ObjectivesTo 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 methodsWomen (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.ResultsMedian concentration of 8-oxodG was 4.7 nmol/L (adjusted for specific weight; range 1.6–13, corresponding to 1.7 μg/g creatinine, range 0.57–4.8) and of total urinary As metabolites (U-As) 290 μg/L (range 94–720; 380 μg/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).ConclusionDespite 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.