[show abstract][hide abstract] ABSTRACT: Whole-grain intake has been reported to be associated with a lower risk of several lifestyle-related diseases such as type 2 diabetes, CVD and some types of cancers. As measurement errors in self-reported whole-grain intake assessments can be substantial, dietary biomarkers are relevant to be used as complementary tools for dietary intake assessment. Alkylresorcinols (AR) are phenolic lipids found almost exclusively in whole-grain wheat and rye products among the commonly consumed foods and are considered as valid biomarkers of the intake of these products. In the present study, we analysed the plasma concentrations of five AR homologues in 2845 participants from ten European countries from a nested case-control study in the European Prospective Investigation into Cancer and Nutrition. High concentrations of plasma total AR were found in participants from Scandinavia and Central Europe and lower concentrations in those from the Mediterranean countries. The geometric mean plasma total AR concentrations were between 35 and 41 nmol/l in samples drawn from fasting participants in the Central European and Scandinavian countries and below 23 nmol/l in those of participants from the Mediterranean countries. The whole-grain source (wheat or rye) could be determined using the ratio of two of the homologues. The main source was wheat in Greece, Italy, the Netherlands and the UK, whereas rye was also consumed in considerable amounts in Germany, Denmark and Sweden. The present study demonstrates a considerable variation in the plasma concentrations of total AR and concentrations of AR homologues across ten European countries, reflecting both quantitative and qualitative differences in the intake of whole-grain wheat and rye.
The British journal of nutrition 02/2014; · 3.45 Impact Factor
[show abstract][hide abstract] ABSTRACT: Accumulating evidences indicate that pulmonary exposure to carbon nanotubes is associated with increased risk of lung diseases, whereas the effect on the vascular system is less studied. We investigated vascular effects of two types of multi-walled carbon nanotubes (MWCNT) in apolipoprotein E(-/-) mice, wild type mice and cultured cells. The ApoE(-/-) mice had accelerated plaque progression in aorta after five intracheal instillations of MWCNT (25.6 µg/mouse weekly for five weeks). The exposure was associated with pulmonary inflammation, lipid peroxidation and increased expression of inflammatory, oxidative stress, DNA repair and vascular activation response genes. The level of oxidatively damaged DNA in lung tissue was unaltered, probably due to increased DNA repair capacities. Despite upregulation of inflammatory genes in the liver, effects on systemic cytokines and lipid peroxidation were minimal. The exposure to MWCNTs in cultured human endothelial cells increased the expression of vascular adhesion molecules (ICAM1 and VCAM1). In co-cultures there was increased adhesion of monocytes to endothelial cells after exposure to MWCNT. The exposure to both types of MWCNT was also associated with increased lipid accumulation in monocytic-derived foam cells, which was dependent on concomitant oxidative stress since the antioxidant N-acetylcysteine inhibited the lipid accumulation. Collectively our results indicate that exposure to MWCNT is associated with accelerated progression of atherosclerosis, which could be related to both increased adherence of monocytes onto the endothelium and oxidative stress-mediated transformation of monocytes to foam cells.
[show abstract][hide abstract] ABSTRACT: Exposure to airborne particulate matter in homes is associated with the risk of cardiovascular diseases and respiratory problems. Due to the extended time people spend at home, reducing the particle concentration in homes may be a means to reduce the risk of cardiovascular diseases and respiratory problems. Use of particle filtration units (PFU's) might be an effective way for rapid removal of indoor PM.
In a randomised cross-over design, the custom built PFU's ran for two weeks in each of two modes: with or without the inclusion of a HEPA filter.
We assessed the association between the concentration levels of particulate matter and building characteristics; and the use of PFU as a way to effectively reduce the levels of PM2.5 indoors.
The results obtained from the study have shown that a small room area, wooden floor material, or the use of gas for cooking is strongly associated with high PM2.5 mass concentrations. Furthermore, the winter period and a location farther from a trafficked street were associated with increased PM2.5 mass. Overall, the use of PFU led to a decrease in the concentrations of PM2.5 of 54.5% (median value).
We assessed the PFU particle-removal efficiency by using the amount of infiltrated air, size of the controlled room and filtration effectiveness.
Building and Environment 01/2014; 73:55–63. · 2.43 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exposure to particulate air pollution increases respiratory and cardiovascular morbidity and mortality, especially in elderly, possibly through inflammation and vascular dysfunction.
We examined potential beneficial effects of indoor air filtration in the homes of elderly, including people taking vasoactive drugs.Forty-eight nonsmoking subjects (51 to 81 years) in 27 homes were included in this randomized, double-blind, crossover intervention study with consecutive two-week periods with or without the inclusion of a high-efficiency particle air filter in re-circulating custom built units in their living room and bedroom. We measured blood pressure, microvascular and lung function and collected blood samples for hematological, inflammation monocyte surface and lung cell damage markers before and at day 2, 7 and 14 during each exposure scenario.
The particle filters reduced the median concentration of PM2.5 from approximately 8 to 4 mug/m3 and the particle number concentration from 7669 to 5352 particles/cm3. No statistically significant effects of filtration as category were observed on microvascular and lung function or the biomarkers of systemic inflammation among all subjects, or in the subgroups taking (n = 11) or not taking vasoactive drugs (n = 37). However, the filtration efficacy was variable and microvascular function was within 2 days significantly increased with the actual PM2.5 decrease in the bedroom, especially among 25 subjects not taking any drugs.
Substantial exposure contrasts in the bedroom and no confounding by drugs appear required for improved microvascular function by air filtration, whereas no other beneficial effect was found in this elderly population.
Environmental Health 12/2013; 12(1):116. · 2.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: Few studies have investigated the association between whole-grain intake and colorectal cancer. Because whole-grain intake estimation might be prone to measurement errors, more objective measures (eg, biomarkers) could assist in investigating such associations.
The association between alkylresorcinols, biomarkers of whole-grain rye and wheat intake, and colorectal cancer incidence were investigated using prediagnostic plasma samples from colorectal cancer case patients and matched control subjects nested within the European Prospective Investigation into Cancer and Nutrition. We included 1372 incident colorectal cancer case patients and 1372 individual matched control subjects and calculated the incidence rate ratios (IRRs) for overall and anatomical subsites of colorectal cancer using conditional logistic regression adjusted for potential confounders. Regional differences (Scandinavia, the Mediterranean, Central Europe) were also explored.
High plasma total alkylresorcinol concentration was associated with lower incidence of distal colon cancer; the adjusted incidence rate ratio of distal colon cancer for the highest vs lowest quartile of plasma total alkylresorcinols was 0.48 (95% confidence interval [CI] = 0.28 to 0.83). An inverse association between plasma total alkylresorcinol concentrations and colon cancer was found for Scandinavian participants (IRR per doubling = 0.83; 95% CI = 0.70 to 0.98). However, plasma total alkylresorcinol concentrations were not associated with overall colorectal cancer, proximal colon cancer, or rectal cancer. Plasma alkylresorcinols concentrations were associated with colon and distal colon cancer only in Central Europe and Scandinavia (ie, areas where alkylresorcinol levels were higher).
High concentrations of plasma alkylresorcinols were associated with a lower incidence of distal colon cancer but not with overall colorectal cancer, proximal colon cancer, and rectal cancer.
[show abstract][hide abstract] ABSTRACT: Air pollutant levels in Denmark are generally moderate due to a windy climate and moderate local emissions. Despite this, a series of epidemiological studies point to air pollution as a cause of severe adverse health effects in the Danish population. Significant relationships between air pollutant levels and negative health outcomes in the Danish population have thus been found for end points like: stroke, lung cancer, chronic obstructive pulmonary disease, asthma in adults, wheeze in infants, asthma hospital admissions in children, diabetes, and vascular function in the elderly. These findings have been possible as a result of combining the unique Danish health registry data with detailed exposure assessments based on routine monitoring data and/or high resolution exposure modelling. In the following we will have focus on exposure assessment methodologies. Some of the airborne pollutants that are not all well described, and for some pollutants the population based assessments are mainly indicative and incomplete. This especially counts for all airborne allergens. Today about 21% of the Danish population suffer from allergenic rhinitis and a proportion of these are affected by aeroallergens that are associated to specific pollen. There are many different species of airborne pollen in our ambient environment and a fraction of these negatively affects human health. However, this information on the exposure of allergenic pollen is either limited or not available. Initiatives have been taken that aim to bring pollen monitoring up to the same level as general air pollution monitoring programmes have today, including new observational methods for exposure estimates and the use of atmospheric models. As already stated the following chapter describes and discusses the applied methodologies and some of the main findings of the Danish studies on air pollution and pollen exposure assessment, and the associated negative health impact in the Danish population.
[show abstract][hide abstract] ABSTRACT: Exposure to particles has been suggested to generate hepatosteatosis by oxidative stress mechanisms. We investigated lipid accumulation in cultured human hepatocytes (HepG2) and rat liver after exposure to four different carbon-based particles. HepG2 cells were exposed to particles for 3h and subsequently incubated for another 18h to manifest lipid accumulation. In an animal model of metabolic syndrome we investigated the association between intake of carbon black (CB, 14nm) particles and hepatic lipid accumulation, inflammation and gene expression of Srebp-1, Fasn and Scd-1 involved in lipid synthesis. There was a concentration-dependent increase in intracellular lipid content after exposure to CB in HepG2 cells, which was only observed after co-exposure to oleic/palmitic acid. Similar results were observed in HepG2 cells after exposure to diesel exhaust particles, fullerenes C60 or pristine single-walled carbon nanotubes. All four types of particles also generated oxidatively damaged DNA, assessed as formamidopyrimidine DNA glycosylase (FPG) sensitive sites, in HepG2 cells after 3h exposure. The animal model of metabolic syndrome showed increased lipid load in the liver after one oral exposure to 6.4mg/kg of CB in lean Zucker rats. This was not associated with increased iNOS staining in the liver, indicating that the oral CB exposure was associated with hepatic steatosis rather than steatohepatitis. The lipid accumulation did not seem to be related to increased lipogenesis because there were unaltered expression levels in both the HepG2 cells and rat livers. Collectively, exposure to particles is associated with oxidative stress and steatosis in hepatocytes.
Toxicology and Applied Pharmacology 10/2013; · 3.98 Impact Factor
[show abstract][hide abstract] ABSTRACT: Particle number (PN) concentrations (10 - 300 nm in size) were continuously measured over a period of ~45 hours in 56 residences of non-smokers in Copenhagen, Denmark. The highest concentrations were measured when occupants were present and awake (geometric mean, GM: 22.3 × 10^3 cm-3), the lowest when the homes were vacant (GM: 6.1 × 10^3 cm-3) or the occupants were asleep (GM: 5.1 × 10^3 cm-3). Diary entries regarding occupancy and particle related activities were used to identify source events and apportion the daily integrated exposure among sources. Source events clearly resulted in increased PN concentrations and decreased average particle diameter. For a given event, elevated particle concentrations persisted for several hours after the emission of fresh particles ceased. The residential daily integrated PN exposure in the 56 homes ranged between 37 × 10^3 and 6.0 × 10^6 particles per cm3•h/day (GM: 3.3 × 10^5 cm-3•h/day). On average, ~90% of this exposure occurred outside of the period from midnight to 6 AM. Source events, especially candle burning, cooking, toasting and unknown activities, were responsible on average for ~65% of the residential integrated exposure (51% without the unknown activities). Candle burning occurred in half of the homes where, on average, it was responsible for almost 60% of the integrated exposure.
[show abstract][hide abstract] ABSTRACT: Exposure to PCBs may be an etiologic factor for breast cancer. The cytochrome P450 1B1 (CYP1B1) and catechol-O-methyltransferase (COMT) enzymes are involved in estrogen metabolism and PCB metabolism, both of which may relate to breast cancer susceptibility. Polymorphisms in genes regulating these enzymes control efficiency. Our objective was to assess whether CYP1B1 and COMT gene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. Neither CYP1B1 Leu432Val polymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of the COMT Val158Met polymorphism, we observed reduced risk for breast cancer amongst hormone replacement therapy using women who were homozygous carriers of the variant allele compared with those carrying the wild-type variant (RR = 0.41; 95% CI: 0.29-0.89). We found no statistically significant interactions between any of the PCB groups and CYP1B1 or COMT polymorphisms on the risk of breast cancer.
International Journal of Environmental Health Research 07/2013; · 1.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The measurement of DNA-repair activity by extracts from cells or tissues by means of the single-cell gel electrophoresis (comet) assay has a high potential to become widely used in biomonitoring studies. We assessed the inter-laboratory variation in reported values of DNA-repair activity on substrate cells that had been incubated with Ro19-8022 plus light to generate oxidatively damaged DNA. Eight laboratories assessed the DNA-repair activity of three cell lines (i.e. one epithelial and two fibroblast cell lines), starting with cell pellets or with cell extracts provided by the coordinating laboratory. There was a large inter-laboratory variation, as evidenced by the range in the mean level of repair incisions between the laboratory with the lowest (0.002 incisions/10(6) bp) and highest (0.988 incisions/10(6) bp) incision activity. Nevertheless, six out of eight laboratories reported the same cell line as having the highest level of DNA-repair activity. The two laboratories that reported discordant results (with another cell line having the highest level of DNA-repair activity) were those that reported to have little experience with the modified comet assay to assess DNA repair. The laboratories were also less consistent in ordering the repair activity of the other two cell lines, probably because the DNA-repair activity by extracts from these cell lines were very similar (on average approximately 60-65% of the cell line with the highest repair capacity). A significant correlation was observed between the repair activity found in the provided and the self-made cell extracts (r=0.71, P<0.001), which indicates that the predominant source for inter-laboratory variation is derived from the incubation of the extract with substrate cells embedded in the gel. Overall, we conclude that the incubation step of cell extracts with the substrate cells can be identified as a major source of inter-laboratory variation in the modified comet assay for base-excision repair.
Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis 07/2013; · 3.90 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: Oxidative stress may be important in carcinogenesis and a possible risk factor for breast cancer. The urinary excretion of oxidatively generated biomolecules, such as 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), represents biomarkers of oxidative stress, reflecting the rate of global damage to DNA in steady state. METHODS: In a nested case-control design we examined associations between urinary excretion of 8-oxodG and risk of breast cancer in a population-based cohort of 24,697 postmenopausal women aged 50-64 year with 3-7 years follow-up. The accruing cases of breast cancer were matched to controls by age at diagnosis, baseline age and hormone replacement therapy (HRT). Spot urine samples collected at entry was analysed for 8-oxodG by HPLC with electrochemical detection. Incidence rate ratio (IRR; 95% confidence intervals) based on 336 matched pairs with all information was estimated per unit increase in 8-oxodG divided by creatinine for all and estrogen receptor (ER) positive and negative breast cancers. RESULTS: There was a borderline significant positive association between 8-oxodG and risk of all breast cancer (IRR: 1.08; 1.00-1.17 per unit increase in nmol/mmol creatinine). This association was significant with respect to the risk of ER positive cancer (IRR: 1.11; 1.01-1.23) and among women not using HRT (IRR: 1.11 (0.97-1.26) or with low dietary iron intake (IRR: 1.10; 1.06-1.37 per unit increase) for all breast cancer. CONCLUSION: We observed positive association between 8-oxodG excretion and risk of especially ER positive breast cancer. Impact: Our results suggest that oxidative stress with damage to DNA is important for the development of breast cancer.
Cancer Epidemiology Biomarkers & Prevention 05/2013; · 4.56 Impact Factor
[show abstract][hide abstract] ABSTRACT: PURPOSE: A high intake of whole grains has been associated with a lower incidence of colorectal cancer, but few studies are available on the association with whole grains from different cereals, for example, wheat, rye and oats, and none has addressed these separately. The objective of this study was to investigate the association between whole-grain intake and colorectal cancer. METHOD: We used data from the large population-based Scandinavian cohort HELGA consisting of 108,000 Danish, Swedish, and Norwegian persons, of whom 1,123 developed colorectal cancer during a median of 11 years of follow-up. Detailed information on daily intake of whole-grain products, including whole-grain bread, crispbread, and breakfast cereals, was available, and intakes of total whole grains and specific whole-grain species (wheat, rye, and oats) were estimated. Associations between these whole-grain variables and the incidence of colorectal cancer were investigated using Cox proportional hazards models. Intake of whole-grain products was associated with a lower incidence of colorectal cancer per 50-g increment (incidence rate ratio [IRR], 0.94; 95 % confidence interval [CI], 0.89, 0.99), and the same tendency was found for total whole-grain intake (IRR pr. 25-g increment, 0.94; 95 % CI, 0.88, 1.01). Intake of whole-grain wheat was associated with a lower incidence of colorectal cancer (IRR for highest versus lowest quartile of intake, 0.66; 95 % CI, 0.51, 0.85), but no statistical significant linear trend was observed (p for trend: 0.18). No significant association was found for whole-grain rye or oats. CONCLUSION: Whole-grain intake was associated with a lower incidence of colorectal cancer.
Cancer Causes and Control 04/2013; · 3.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: It has been suggested that anthocyanin-rich foods may exert antioxidant effects and improve vascular function as demonstrated mainly in vitro and in the animal model. Blueberries are rich sources of anthocyanins and we hypothesized that their intake could improve cell protection against oxidative stress and affect endothelial function in humans. The aim of the study was to investigate the effect of one portion (300 g) of blueberries on selected markers of oxidative stress and antioxidant protection (endogenous and oxidatively induced DNA damage) and of vascular function (changes in peripheral arterial tone and plasma nitric oxide levels) in male subjects. In a randomized cross-over design, separated by a wash out period ten young volunteers received one portion of blueberries ground by blender or one portion of a control jelly. Before and after consumption (at 1, 2, and 24 hours), blood samples were collected and used to evaluate anthocyanin absorption (through mass spectrometry), endogenous and H2O2-induced DNA damage in blood mononuclear cells (through the comet assay), and plasma nitric oxide concentrations (through a fluorometric assay). Peripheral arterial function was assessed by means of Endo-PAT 2000. Blueberries significantly reduced (P < .01) H2O2-induced DNA damage (-18%) 1 hour after blueberry consumption compared to control. No significant differences were observed for endogenous DNA damage, peripheral arterial function and nitric oxide levels after blueberry intake. In conclusion, one portion of blueberries seems sufficient to improve cell antioxidant defense against DNA damage, but further studies are necessary to understand their role on vascular function.
Nutrition research (New York, N.Y.) 03/2013; 33(3):220-227. · 1.20 Impact Factor
[show abstract][hide abstract] ABSTRACT: The alkaline comet assay is an established, sensitive method extensively used in biomonitoring studies. This method can be modified to measure a range of different types of DNA damage. However, considerable differences in the protocols used by different research groups affect the inter-laboratory comparisons of results. The aim of this study was to assess the inter-laboratory, intra-laboratory, sample and residual (unexplained) variations in DNA strand breaks and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites measured by the comet assay by using a balanced Latin square design. Fourteen participating laboratories used their own comet assay protocols to measure the level of DNA strand breaks and FPG-sensitive sites in coded samples containing peripheral blood mononuclear cells (PBMC) and the level of DNA strand breaks in coded calibration curve samples (cells exposed to different doses of ionising radiation) on three different days of analysis. Eleven laboratories found dose-response relationships in the coded calibration curve samples on two or three days of analysis, whereas three laboratories had technical problems in their assay. In the coded calibration curve samples, the dose of ionising radiation, inter-laboratory variation, intra-laboratory variation and residual variation contributed to 60.9, 19.4, 0.1 and 19.5%, respectively, of the total variation. In the coded PBMC samples, the inter-laboratory variation explained the largest fraction of the overall variation of DNA strand breaks (79.2%) and the residual variation (19.9%) was much larger than the intra-laboratory (0.3%) and inter-subject (0.5%) variation. The same partitioning of the overall variation of FPG-sensitive sites in the PBMC samples indicated that the inter-laboratory variation was the strongest contributor (56.7%), whereas the residual (42.9%), intra-laboratory (0.2%) and inter-subject (0.3%) variations again contributed less to the overall variation. The results suggest that the variation in DNA damage, measured by comet assay, in PBMC from healthy subjects is assay variation rather than variation between subjects.
[show abstract][hide abstract] ABSTRACT: Abstract Exposure to combustion-derived particles, quartz and asbestos is associated with increased levels of oxidized and mutagenic DNA lesions. The aim of this survey was to critically assess the measurements of oxidatively damaged DNA as marker of particle-induced genotoxicity in animal tissues. Publications based on non-optimal assays of 8-oxo-7,8-dihydroguanine by antibodies and/or unrealistically high levels of 8-oxo-7,8-dihydroguanine (suggesting experimental problems due to spurious oxidation of DNA) reported more induction of DNA damage after exposure to particles than did the publications based on optimal methods. The majority of studies have used single intracavitary administration or inhalation with dose rates exceeding the pulmonary overload threshold, resulting in cytotoxicity and inflammation. It is unclear whether this is relevant for the much lower human exposure levels. Still, there was linear dose-response relationship for 8-oxo-7,8-dihydroguanine in lung tissue without obvious signs of a threshold. The dose-response function was also dependent on chemical composition and other characteristics of the administered particles, whereas dependence on species and strain could not be equivocally determined. Roles of cytotoxicity or inflammation for oxidatively induced DNA damage could not be documented or refuted. Studies on exposure to particles in the gastrointestinal tract showed consistently increased levels of 8-oxo-7,8-dihydroguanine in the liver. Collectively, there is evidence from animal experimental models that both pulmonary and gastrointestinal tract exposure to particles are associated with elevated levels of oxidatively damaged DNA in the lung and internal organs. However, there is a paucity of studies on pulmonary exposure to low doses of particles that are relevant for hazard/risk assessment.
Critical Reviews in Toxicology 02/2013; 43(2):96-118. · 6.25 Impact Factor
[show abstract][hide abstract] ABSTRACT: Cardiovascular disease is the number one cause of death globally and air pollution can be a contributing cause. Acute myocardial infarction and cardiac arrest are frequent manifestations of coronary heart disease. The objectives of the study were to investigate the association between 4 657 out-of-hospital cardiac arrests (OHCA) and hourly and daily outdoor levels of PM(10), PM(2.5), coarse fraction of PM (PM(10-2.5)), ultrafine particle proxies, NO(x), NO(2), O(3) and CO in Copenhagen, Denmark, for the period 2000-2010. Susceptible groups by age and sex was also investigated. A case-crossover design was applied. None of the hourly lags of any of the pollutants were significantly associated with OHCA events. The strongest association with OHCA events was observed for the daily lag4 of PM(2.5), lag3 of PM(10), lag3 of PM(10-2.5), lag3 of NO(x) and lag4 of CO. An IQR increase of PM(2.5) and PM(10) was associated with a significant increase of 4% (95% CI: 0%; 9%) and 5% (95% CI: 1%; 9%) in OHCA events with 3 days lag, respectively. None of the other daily lags or other pollutants was significantly associated with OHCA events. Adjustment for O(3) slightly increased the association between OHCA and PM(2.5) and PM(10). No susceptible groups were identified.
PLoS ONE 01/2013; 8(1):e53684. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Increased brain tumour incidence over recent decades may reflect improved diagnostic methods and clinical practice, but remain unexplained. Although estimated doses are low a relationship between radon and brain tumours may exist.
To investigate the long-term effect of exposure to residential radon on the risk of primary brain tumour in a prospective Danish cohort.
During 1993-1997 we recruited 57,053 persons. We followed each cohort member for cancer occurrence from enrolment until 31 December 2009, identifying 121 primary brain tumour cases. We traced residential addresses from 1 January 1971 until 31 December 2009 and calculated radon concentrations at each address using information from central databases regarding geology and house construction. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and 95% confidence intervals (CI) for the risk of primary brain tumours associated with residential radon exposure with adjustment for age, sex, occupation, fruit and vegetable consumption and traffic-related air pollution. Effect modification by air pollution was assessed.
Median estimated radon was 40.5 Bq/m(3). The adjusted IRR for primary brain tumour associated with each 100 Bq/m(3) increment in average residential radon levels was 1.96 (95% CI: 1.07; 3.58) and this was exposure-dependently higher over the four radon exposure quartiles. This association was not modified by air pollution.
We found significant associations and exposure-response patterns between long-term residential radon exposure radon in a general population and risk of primary brain tumours, adding new knowledge to this field. This finding could be chance and needs to be challenged in future studies.
PLoS ONE 01/2013; 8(9):e74435. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers data interpretation, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyse 8-oxodG-spiked phosphate buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (rp 0.67 - 0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity. The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assays, and cannot determine absolute levels of 8-oxodG. Use of standardised calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.