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Burning candles at home emit small particles and gases that pollute indoor air. Exposure to fine particles in outdoor air has been convincingly linked to cardiovascular and respiratory events, while the associations with fine and ultrafine particles from candle burning remain unexplored. We examined the association between the use of candles and incident cardiovascular and respiratory events. We collected data on 6757 participants of the Copenhagen Aging and Midlife Biobank cohort recruited in 2009 and followed them up for the first hospital contact for incident cardiovascular and respiratory events until 2018. We investigated an association between the self‐reported frequency of candle use in wintertime and cardiovascular and respiratory events, using Cox regression models adjusting for potential confounders. During follow‐up, 1462 and 834 were admitted for cardiovascular and respiratory events, respectively. We found null associations between candle use and a hospital contact due to cardiovascular and respiratory events, with hazard ratios (HRs) and 95% confidence intervals (CI) of 0.97 (95% CI: 0.84, 1.11) and 0.98 (95% CI: 0.81, 1.18), respectively, among those using candles >4 times/week compared with <1 time/week. For cause‐specific cardiovascular diseases, HRs were 1.10 (95% CI: 0.85, 1.43) for ischemic heart disease and 1.18 (95% CI: 0.77, 1.81) for myocardial infarction. For chronic obstructive pulmonary disease, HR was 1.26 (95% CI: 0.81, 1.97). We found no statistically significant associations between candle use and the risk of cardiovascular and respiratory events. Studies with improved exposure assessments are warranted. [ABSTRACT FROM AUTHOR]

Background: Although exposure to UV radiation is the major risk factor for skin cancer, theoretical models suggest that radon exposure can contribute to risk, and this is supported by ecological studies. We sought to confirm or refute an association between long-term exposure to residential radon and the risk for malignant melanoma (MM) and non-melanoma skin cancer (NMSC) using a prospective cohort design and long-term residential radon exposure. Methods: During 1993–1997, we recruited 57,053 Danish persons and collected baseline information. We traced and geocoded all residential addresses of the cohort members and calculated radon concentrations at each address lived in from 1 January 1971 until censor date. Cox proportional hazards models were used to estimate incidence rate-ratios (IRR) and confidence intervals (CI) for the risk associated with radon exposure for NMSC and MM, and effect modification was assessed. Results: Over a mean follow-up of 13.6 years of 51,445 subjects, there were 3,243 cases of basal cell carcinoma (BCC), 317 cases of squamous cell carcinoma (SCC) and 329 cases of MM. The adjusted IRRs per 100 Bq/m3 increase in residential radon levels for BCC, SCC and MM were 1.14 (95% CI: 1.03, 1.27), 0.90 (95% CI: 0.70, 1.37) and 1.08 (95% CI: 0.77, 1.50), respectively. The association between radon exposure and BCC was stronger among those with higher socio-economic status and those living in apartments at enrollment. Conclusion and Impact: Long-term residential radon exposure may contribute to development of basal cell carcinoma of the skin. We cannot exclude confounding from sunlight and cannot conclude on causality, as the relationship was stronger amongst persons living in apartments and non-existent amongst those living in single detached homes. [ABSTRACT FROM AUTHOR]

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 whetherCYP1B1andCOMTgene polymorphisms modulate the effect of PCBs in breast cancer risk, among postmenopausal Danish women. NeitherCYP1B1 Leu432Valpolymorphisms nor adipose tissue PCBs were independently associated with breast cancer risk. When assessing the independent effect of theCOMT Val158Metpolymorphism, 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 andCYP1B1orCOMTpolymorphisms on the risk of breast cancer. [ABSTRACT FROM PUBLISHER]

A broad scientific community is involved in investigations aimed at delineating the mechanisms of formation and cellular processing of oxidatively generated damage to nucleic acids. Perhaps as a consequence of this breadth of research expertise, there are nomenclature problems for several of the oxidized bases including 8-oxo-7,8-dihydroguanine (8-oxoGua), a ubiquitous marker of almost every type of oxidative stress in cells. Efforts to standardize the nomenclature and abbreviations of the main DNA degradation products that arise from oxidative pathways are reported. Information is also provided on the main oxidative radicals, non-radical oxygen species, one-electron agents and enzymes involved in DNA degradation pathways as well in their targets and reactivity. A brief classification of oxidatively generated damage to DNA that may involve single modifications, tandem base modifications, intrastrand and interstrand cross-links together with DNA-protein cross-links and base adducts arising from the addition of lipid peroxides breakdown products is also included. [ABSTRACT FROM AUTHOR]

Abstract: Toxicological effects of wood smoke particles are less investigated than traffic-related combustion particles. We investigated the effect of wood smoke particles, generated by smouldering combustion conditions, on human umbilical endothelial cells (HUVECs) co-cultured with or without monocytic THP-1 cells. Standard reference material (SRM) 2975 diesel exhaust particles were used as benchmark particles. Wood smoke particles at 50μg/ml or 100μg/ml caused adhesion of THP-1 monocytes onto HUVECs in co-cultures, whereas SRM2975 had no such effect. Both types of particles from 1μg/ml increased VCAM-1 expression on HUVECs in mono-cultures. However, only the exposure to wood smoke particles was associated with increased expression of TNF and IL8 mRNA in THP-1 cells. We found no effect on the intracellular production of reactive oxygen species by the fluorescent probe DCFH-DA, whereas especially the wood smoke particles caused increased level of DNA strand breaks and oxidised guanines at concentrations with low cytotoxicity. In conclusion, our results indicate that the adherence of monocytes on endothelial cells in wood smoke particle exposed cultures depend on activation of both cell types. [Copyright &y& Elsevier]

Abstract: Oxidatively damaged DNA may be important in carcinogenesis. 8-Oxo-7,8-dihydroguanine (8-oxoGua) is an abundant and mutagenic lesion excised by oxoguanine DNA glycosylase 1 (OGG1) and measurable in urine or plasma by chromatographic methods with electrochemical or mass spectrometric detectors, reflecting the rate of damage in steady state. A common genetic OGG1 variant may affect the activity and was associated with increased levels of oxidized purines in leukocytes without apparent effect on 8-oxoGua excretion or major change in cancer risk. 8-OxoGua excretion has been associated with exposure to air pollution, toxic metals, tobacco smoke and low plasma antioxidant levels, whereas fruit and vegetable intake or dietary interventions showed no association. In rodent studies some types of feed may be source of 8-oxoGua in collected urine. Of cancer therapies, cisplatin increased 8-oxoGua excretion, whereas radiotherapy only showed such effects in experimental animals. Case-control studies found high excretion of 8-oxoGua in relation to cancer, dementia and celiac disease but not hemochromatosis, although associations could be a consequence rather than reflecting causality of disease. One prospective study found increased risk of developing lung cancer among non-smokers associated with high excretion of 8-oxoGua. Urinary excretion of 8-oxoGua is a promising biomarker of oxidatively damaged DNA. [Copyright &y& Elsevier]

Abstract: Oxidative damage to guanine (8-oxoGua) is one of the most abundant lesions induced by oxidative stress and documented mutagenic. 8-Oxoguanine DNA glycosylase 1 (OGG1) removes 8-oxoGua from DNA by excision. The urinary excretion of 8-oxoGua is a biomarker of exposure, reflecting the rate of damage in the steady state. The aim of this study was to investigate urinary 8-oxoGua as a risk factor for lung cancer. In a nested case-cohort design we examined associations between urinary excretion of 8-oxoGua and risk of lung cancer as well as potential interaction with the OGG1 Ser326Cys polymorphism in a population-based cohort of 25,717 men and 27,972 women aged 50–64years with 3–7years follow-up. We included 260 cases with lung cancer and a subcohort of 263 individuals matched on sex, age, and smoking duration for comparison. Urine collected at entry was analysed for 8-oxoGua by HPLC with electrochemical detection. There was no significant effect of smoking or OGG1 genotype on the excretion of 8-oxoGua. Overall the incidence rate ratio (IRR) (95% confidence interval) of lung cancer was 1.06 (0.97–1.15) per doubling of 8-oxoGua excretion. The association between lung cancer risk and 8-oxoGua excretion was significant among men [IRR: 1.17 (1.03–1.31)], never-smokers [IRR: 9.94 (1.04–94.7)], and former smokers [IRR: 1.19 (1.07–1.33)]. There was no significant interaction with the OGG1 genotype, although the IRR was 1.14 (0.98–1.34) among subjects homozygous for Cys326. The association between urinary 8-oxoGua excretion and lung cancer risk among former and never-smokers suggests that oxidative stress with damage to DNA is important in this group. [Copyright &y& Elsevier]

Wood combustion is a significant source of ambient particulate matter (PM) in many regions of the world. Exposure occurs through inhalation or ingestion after deposition of wood smoke particulate matter (WSPM) on crops and food. We investigated effects of ambient PM and WSPM by intragastric or intratracheal exposure in terms of oxidative stress, inflammation, genotoxicity, and DNA repair after 24 h in liver and lung tissue of rats. Rats were exposed to WSPM from high or low oxygen combustion and ambient PM collected in areas with and without many operating wood stoves or carbon black (CB) at the dose of 0.64 mg/kg body weight. The levels of 8-oxo-7,8-dihydro-2′-deoxyguanosine, 1,N6-etheno-2′-deoxyadenosine, and 1-N2-etheno-2′-deoxyguanosine (ɛdG) were significantly increased with 23% (95% confidence interval [CI]: 0.1–45%), 54% (95% CI:18–90%), and 73% (95% CI: 31–134%) in the liver of rats exposed orally to CB, respectively. Rats orally exposed to PM from the wood stove area and low oxygen combustion WSPM (LOWS) had 35% (95% CI: 0.1–71%) and 45% (95% CI: 10–82%) increased levels of ɛdG in the liver, respectively. No significant differences were observed for bulky DNA adducts. Increased gene expression of proinflammatory cytokines, heme oxygenase-1, and oxoguanine DNA glycosylase 1 was observed in the liver following intragastric exposure and in the lung following instillation in particular of LOWS. Exposure to LOWS also increased the proportion of neutrophils in BAL fluid. These results indicate that WSPM and CB exert the strongest effect in terms of oxidative stress–induced response, inflammation, and genotoxicity in the organ closest to the port of entry. [ABSTRACT FROM AUTHOR]

Background: Air pollution is thought to exert health effects through oxidative stress, which causes damage to DNA and lipids. Objective: We determined whether levels of oxidatively damaged DNA and lipid peroxidation products in cells or bodily fluids from humans are useful biomarkers of biologically effective dose in studies of the health effects of exposure to particulate matter (PM) from combustion processes. Data sources: We identified publications that reported estimated associations between environ­mental exposure to PM and oxidative damage to DNA and lipids in PubMed and EMBASE. We also identified publications from reference lists and articles cited in the Web of Science. Data extraction: For each study, we obtained information on the estimated effect size to calcu­late the standardized mean difference (unitless) and determined the potential for errors in exposure assessment and analysis of each of the biomarkers, for total and stratified formal meta-analyses. data synthesis: In the meta-analysis, the standardized mean differences (95% confidence interval) between exposed and unexposed subjects for oxidized DNA and lipids were 0.53 (0.29-0.76) and 0.73 (0.18-1.28) in blood and 0.52 (0.22-0.82) and 0.49 (0.01-0.97) in urine, respectively. The standardized mean difference for oxidized lipids was 0.64 (0.07-1.21) in the airways. Restricting analyses to studies unlikely to have substantial biomarker or exposure measurement error, stud­ies likely to have biomarker and/or exposure error, or studies likely to have both sources of error resulted in standardized mean differences of 0.55 (0.19-0.90), 0.66 (0.37-0.95), and 0.65 (0.34-0.96), respectively. conclusions: Exposure to combustion particles is consistenly associated with oxidatively damaged DNA and lipids in humans, suggesting that it is possible to use these measurements as biomarkers of biologically effective dose. [ABSTRACT FROM AUTHOR]

Abstract: Genotoxic effects of traffic-generated particulate matter (PM) are well described, whereas little data are available on PM from combustion of biomass and wood, which contributes substantially to air pollution world wide. The aim of this study was to compare the genotoxicity of wood smoke particulate matter (WSPM), authentic traffic-generated particles, mineral PM and standard reference material (SRM2975) of diesel exhaust particles in human A549 lung epithelial and THP-1 monocytic cell lines. DNA damage was measured as strand breaks (SB) and formamidopyrimidine DNA glycosylase (FPG) sites by the comet assay, whereas cell cytotoxicity was determined as lactate dehydrogenase release. The exposure to WSPM generated SB and FPG sites in both cell lines at concentrations from 2.5 or 25μg/ml, which were not cytotoxic. Compared to all other studied particles, WSPM generated greater responses in terms of both SB and FPG sites. Organic extracts of WSPM and SRM2975 elicited higher levels of SB than native and washed PM at 25 and 100μg/ml, whereas assay saturation precluded reliable assessment of FPG sites. During a 6h post-exposure period, in which the medium with PM had been replaced by fresh medium, 60% of the DNA lesions generated by WSPM were removed. In conclusion, WSPM generated more DNA damage than traffic-generated PM per unit mass in human cell lines, possibly due to the high level of polycyclic aromatic hydrocarbons in WSPM. This suggests that exposure to WSPM might be more hazardous than PM collected from vehicle exhaust with respect to development of lung cancer. [Copyright &y& Elsevier]

Oxidative-stress-induced damage to DNA includes a multitude of lesions, many of which are mutagenic and have multiple roles in cancer and aging. Many lesions have been characterized by MS-based methods after extraction and digestion of DNA. These preparation steps may cause spurious base oxidation, which is less likely to occur with methods such as the comet assay, which are based on nicking of the DNA strand at modified bases, but offer less specificity. The European Standards Committee on Oxidative DNA Damage has concluded that the true levels of the most widely studied lesion, 8-oxodG (8-oxo-7,8-dihydro-2′- deoxyguanosine), in cellular DNA is between 0.5 and 5 lesions per 106 dG bases. Base excision repair of oxidative damage to DNA can be assessed by nicking assays based on oligonucleotides with lesions or the comet assay, by mRNA expression levels or, in the case of, e.g., OGG1 (8-oxoguanine DNA glycosylase 1), responsible for repair of 8-oxodG, by genotyping. Products of repair in DNA or the nucleotide pool, such as 8-oxodG, excreted into the urine can be assessed by MS-based methods and generally reflects the rate of damage. Experimental and population-based studies indicate that many environmental factors, including particulate air pollution, cause oxidative damage to DNA, whereas diets rich in fruit and vegetables or antioxidant supplements may reduce the levels and enhance repair. Urinary excretion of 8-oxodG, genotype and expression of OGG1 have been associated with risk of cancer in cohort settings, whereas altered levels of damage, repair or urinary excretion in case-control settings may be a consequence rather than the cause of the disease. [ABSTRACT FROM AUTHOR]

Oxidative damage to DNA is regarded as an important step in carcinogenesis. These lesions may arise as a consequence of exposure to xenobiotics, but are also generated as a consequence of endogenous generation of oxidizing compounds. Measurements of oxidative damage to guanines, such as 8-oxo-7, 8-dihydroguanine (8-oxodG) are increasingly being regarded as reliable biomarkers of oxidative stress and they may have a predictive value of cancer risk, although this needs to be established independently in several cohort studies. A survey of intervention studies of the ingestion of antioxidant-containing foods or tablets of antioxidants indicate that about one-third of the studies reported a protective effect in terms of lower levels of oxidative damage to DNA in white blood cells or decreased urinary excretion of 8-oxodG. Although firm conclusions cannot be reached, there appears to be links between ingestion of antioxidants, oxidative damage to DNA, and risk of cancer. [ABSTRACT FROM AUTHOR]

Abstract: Oxidative DNA damage is believed to be implicated in lung carcinogenesis. 8-OxodG is a mutagenic and abundant oxidative modification induced in DNA. OGG1, NEIL1 and MUTYH are all involved in the repair and prevention of 8-oxodG-derived mutations and may be up-regulated by oxidative stress. The polymorphism OGG1 Ser326Cys has in some studies been associated with risk of lung cancer. In a population-based cohort of 57,053 Danes, we examined associations between mRNA levels of OGG1, NEIL1, MUTYH and NUDT in buffy coat material and subsequent lung cancer risk. 260 cases with lung cancer were identified and a sub-cohort of 263 individuals was matched on sex, age and smoking duration. We found that OGG1 mRNA levels in healthy individuals were not associated with risk of subsequent getting lung cancer. However, subjects with the OGG1 Cys326/Cys326 genotype had a higher expression level of OGG1 mRNA than wildtype-allele carriers. For homozygous Cys326 carriers, the incidence rate ratio (IRR) was 1.51 (95% CI: 1.09–2.08) for a doubling of the OGG1 mRNA level and there was a statistically significant interaction between the genotype and mRNA level. Among never-smokers, the IRR was 4.29 (1.09–16.9) per doubling of the OGG1 mRNA level, which was not found among smokers. Furthermore, we found a positive correlation between OGG1 mRNA expression and urinary excretion of 8-oxodG (RS=0.18; p <0.005). NUDT1 mRNA levels were omitted due to low and unreliable expression levels. The results suggest that OGG1 mRNA levels should be regarded as a biomarker of exposure to oxidative stress with induction of DNA rather than a marker of inborn DNA repair capacity. [Copyright &y& Elsevier]

The transition metal iron is catalytically highly active in vitro, and not surprisingly, body iron has been suggested to promote oxidative stress in vivo. In the current analysis we studied the association of serum ferritin concentration and serum soluble transferrin receptor concentration with daily urinary 8-hydroxydeoxyguanosine excretion, a marker of oxidative stress, in 48 mildly dyslipidemic men in East Finland. In multivariate linear regression analyses allowing for age, smoking, body mass index and physical exercise, serum ferritin concentration predicted the excretion rate at B = 0.17 (95% CI 0.08-0.26, P = 0.001), and serum soluble transferrin receptor to ferritin concentration ratio (TfR/ferritin) predicted the excretion rate at B = - 0.13 (95% CI - 0.21 to - 0.05, P = 0.002). Our data suggest that body iron contributes to excess oxidative stress already at non-iron overload concentrations in these subjects. [ABSTRACT FROM AUTHOR]

Abstract: Many biomonitoring studies have investigated the role of antioxidants in reducing oxidatively generated DNA damage in urine and white blood cells. A collective interpretation is difficult because many studies lack sufficient control and have unreasonably high baseline levels of oxidatively damaged DNA. In a survey of this antioxidant hypothesis, we identified 139 cross-sectional and intervention studies. Restricted selection criteria with exclusion of studies having suboptimal design or unreasonably high baseline damage level provided 85 eligible studies for analysis. Ten of the 27 cross-sectional studies reported negative correlations between antioxidants and oxidatively damaged DNA, albeit with correlation coefficients explaining less than 20% of the variance. Sixty-two intervention studies reported mixed results, which did not depend on sample size or duration of the intervention. Reduced levels of oxidatively damaged DNA in white blood cells and urine were reported in far more studies than expected by chance alone. Supplementation with antioxidant-rich foods was more effective than that with single antioxidants in lowering urinary excretion of oxidatively damage DNA. In conclusion, this survey indicates that ingestion of antioxidants may be associated with reduced level of DNA damage in white blood cells and urine of humans, albeit the effect is lower than previously expected. [Copyright &y& Elsevier]

Epidemiological studies have found negative associations between human health and particulate matter in urban air. In most studies outdoor monitoring of urban background has been used to assess exposure. In a field study, personal exposure as well as bedroom, front door and background concentrations of PM2.5, black smoke (BS), and nitrogen dioxide (NO2) were measured during 2-day periods in 30 subjects (20–33 years old) living and studying in central parts of Copenhagen. The measurements were repeated in the four seasons. Information on indoor exposure sources such as environmental tobacco smoke (ETS) and burning of candles was collected by questionnaires. The personal exposure, the bedroom concentration and the front door concentration was set as outcome variable in separate models and analysed by mixed effect model regression methodology, regarding subject levels as a random factor. Seasons were defined as a dichotomised grouping of outdoor temperature (above and below 8°C). For NO2 there was a significant association between personal exposure and both the bedroom, the front door and the background concentrations, whereas for PM2.5 and BS only the bedroom and the front door concentrations, and not the background concentration, were significantly associated to the personal exposure. The bedroom concentration was the strongest predictor of all three pollution measurements. The association between the bedroom and front door concentrations was significant for all three measurements, and the association between the front door and the background concentrations was significant for PM2.5 and NO2, but not for BS, indicating greater spatial variation for BS than for PM2.5 and NO2. For NO2, the relationship between the personal exposure and the front door concentration was dependent upon the “season”, with a stronger association in the warm season compared with the cold season, and for PM2.5 and BS the same tendency was seen. Time exposed to burning of candles was a significant predictor of personal PM2.5, BS and NO2 exposure, and time exposed to ETS only associated with personal PM2.5 exposure. These findings imply that the personal exposure to PM2.5, BS and NO2 depends on many factors besides the outdoor levels, and that information on, for example, time of season or outdoor temperature and residence exposure, could improve the accuracy of the personal exposure estimation.Journal of Exposure Analysis and Environmental Epidemiology (2005) 15, 413–422. doi:10.1038/sj.jea.7500419; published online 26 January 2005 [ABSTRACT FROM AUTHOR]

Berry extracts possess antioxidant activity in cell free systems, whereas cell culture and animal experimental systems have produced mixed outcomes. Our aim was to investigate the effects of blackcurrant juice and specifically blackcurrant anthocyanins on the steady state level of oxidative DNA damage in mononuclear blood cells (MNBC) of humans, determined as strand breaks (SB) as well as endonuclease III (Endo III) and formamidopyrimidine DNA glycosylase (Fpg) sensitive sites by the comet assay. Fifty-seven healthy humans completed a 3-week controlled parallel intervention study with three groups randomized to supplementation with blackcurrant juice, anthocyanin drink, or a control drink. The daily doses ranged from 475 to 1000 ml/d according to body weight (mean anthocyanin intakes in blackcurrant juice and anthocyanin drink groups were 397 and 365 g/d, respectively) and they were ingested during three daily meals while all volunteers were on the same strictly controlled low-flavonoid diet. Fasting venous blood samples were obtained at baseline and after 3-week of supplementation. The baseline level of oxidative DNA damage was low (e.g. less than 200 Fpg lesions per diploid cell). Fpg sensitive sites increased during the intervention within the blackcurrant juice group, whereas there were no differences between treatments in any of the DNA damage markers. In conclusion, this study shows that even large amounts of dietary antioxidants did not decrease the already low steady state levels of oxidative DNA damage in healthy adequately nourished humans. [Copyright &y& Elsevier]

Cells are constantly exposed to oxidants from metabolic and other biochemical reactions as well as external factors, suggesting that DNA repair systems and nutritional antioxidants are important determinants for low levels of DNA damage and cancer risk. The effects of single antioxidants, as well as various vegetables, fruits and carotenoid- and polyphenolic-rich products, have been assessed with biomarkers, mainly including DNA damage in white blood cells (WBC), urinary excretion of oxidized bases and nucleosides and DNA repair capacity. The basal levels of oxidative DNA damage, and effects of the interventions have been rather variable, possibly reflecting differences in the populations, regimens, and the type of assays. In general, single dose antioxidant interventions have shown protective effects with respect to WBC DNA oxidation. Studies with continuous ingestion of antioxidants show mixed results with respect to effects on oxidative DNA damage in WBC, possibly due to various problems with design, statistical power and period effects. Studies with only male subjects appear to show consistent antioxidant effects in terms of reduced levels of oxidized pyrimidines. Investigations of oxidatively stressed subjects, e.g. HIV-infected patients or diabetics, suggest beneficial outcomes in populations with high initial levels of oxidative DNA damage. Recent research on the effect of antioxidants on DNA repair enzymes suggest effects in terms of increased removal of oxidized purines, whereas mRNA levels of the relevant DNA repair genes appears to be unaffected by an antioxidant-rich diet. In the future, care should be taken with respect to design of intervention studies and considerations of gender effect, genotypes of defence enzymes as well as DNA repair capacity. [Copyright &y& Elsevier]

Background: Oxidative stress and related DNA damage in human sperm may be important for fecundity and pregnancy outcome.Methods: We studied the level of oxidative DNA damage in terms of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in sperm DNA among 225 first-pregnancy planners. Over the six menstrual cycle follow-up time, after cessation of contraception, 135 pregnancies were conceived.Results: The likelihood of pregnancy occurring in a single menstrual cycle was inversely associated with the 8-oxodG level (P < 0.01). The odds ratio of pregnancy in each of the first three or all six follow-up menstrual cycles was 0.42 (0.23-0.78; 95% CI) and 0.61 (0.36-0.91) per unit increase in the log 8-oxodG/100 000 dG ratio after adjustment for potential confounders, (including sperm concentration) respectively. The intra-individual coefficient of variation of 8-oxodG in 2-6 monthly repeated sperm samples from 116 men was 19% for the 8-oxodG/dG ratio, whereas the inter-individual coefficient of variation was 49%. The 8-oxodG level was not significantly associated with smoking, consumption of alcohol or caffeine, exposure to welding fumes or the plasma levels of sex hormones.Conclusions: The data suggest that oxidative damage to sperm DNA influences fecundity and the level of damage is relatively constant within an individual and not influenced by smoking. [ABSTRACT FROM AUTHOR]

We investigated the interaction of BZ and lipolysaccharide (LPS), a well-known inflammation-promoting agent, in wild-type and inducible nitrogen oxide synthase (iNOS) knockout mice. BZ generated DNA strand breaks (SB) in the liver of both wild-type and iNOS-deficient mice. In the bone marrow (BM) BZ and LPS generated SB only in wild-type mice. The effects were additive, suggesting that both a redox cycling and an iNOS-dependent pathway may be involved. Formamidopyrimidine DNA glycosylase sensitive sites were elevated by BZ in the BM in both types of mice, whereas endonuclease III sensitive sites were not affected by any treatment. Since BZ is associated with leukemia in humans, it suggests that oxidative DNA base damage rather than SB may be important in the development of leukemia. [Copyright &y& Elsevier]

Extreme exercise increases oxygen uptake with a potential for increased formation of reactive oxygen species. Damage to biomolecules may occur if such an increase exceeds the protective capacity of antioxidant defence mechanisms. Vigorous exercise amounting to ~ 10 h a day for 30 days increased the rate of oxidative DNA modification by 33% (95% confidence limits, 3-67%; P < 0.02) in 20 men owing to the urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine, an oxidatively modified deoxynucleoside originating from nuclear DNA repair, oxidation of the nucleotide pool from mitochondrial DNA and/or from cell turnover. Oxidative stress to DNA points to a risk for the development of cancer and premature ageing from extreme exercise. [ABSTRACT FROM AUTHOR]

A widely used method for estimating fine scale long-term spatial variation in air pollution, especially for epidemiology studies, is land use regression (LUR) modeling using fixed off-road monitors. More recently, LUR models have been developed using data from mobile monitors that repeatedly measure road pollutants and mixed-effects modeling. Here, nitrogen dioxide (NO2) and black carbon (BC) predictions from two independent models were compared across streets (defined as 30–60 m road segments) (N = 30,312) and residences (N = 76,752) in Copenhagen, Denmark. The first model was Google Street View (GSV)-based mixed-effects LUR models (Google-MM) that predicted 2019 mean NO2 and BC levels, and the second was European-wide (EUW) LUR models that predicted annual mean 2010 levels at 100 m spatial resolution. Across street segments, the Spearman correlation coefficient between the 2019 NO2 from Google-MM-LUR and 2010 NO2 from EUW-LUR was 0.66, while at residences, this was 0.60. For BC, these were 0.51 across street segments and 0.40 at the residential level. The ratio of percentile 97.5 to 2.5 for NO2 across the study area streets using Google-MM NO2 was 4.5, while using EUW-LUR, this was 2.1. These NO2 ratios at residences were 3.1 using Google-MM LUR, and 1.7 using EUW-LUR. Such ratios for BC across street segments were 3.4 using Google-MM LUR and 2.3 using EUW-LUR, while at the residential level, they were 2.4 and 1.9, respectively. In conclusion, Google-MM-LUR NO2 for 2019 was moderately correlated with EUW-LUR NO2 developed in 2010 across Copenhagen street segments and residences. For BC, while Google-MM-LUR was moderately correlated with EUW-LUR across Copenhagen streets, the correlation was lower at the residential level. Overall, Google-MM-LUR revealed larger spatial contrasts than EUW-LUR. [ABSTRACT FROM AUTHOR]

It has been established that ingestion of a high-fat diet increases the blood levels of lipopolysaccharides (LPS) from Gram-negative bacteria in the gut. Obesity is characterised by low-grade systemic and adipose tissue inflammation. This is suggested to be implicated in the metabolic syndrome and obesity. In the present review, we hypothesise that LPS directly and indirectly participates in the inflammatory reaction in adipose tissue during obesity. The experimental evidence shows that LPS is involved in the transition of macrophages from the M2 to the M1 phenotype. In addition, LPS inside adipocytes may activate caspase-4/5/11. This may induce a highly inflammatory type of programmed cell death (i.e. pyroptosis), which also occurs after infection with intracellular pathogens. Lipoproteins with or without LPS are taken up by adipocytes. Large adipocytes are more metabolically active and potentially more exposed to LPS than small adipocytes are. Thus, LPS might be involved in defining the adipocyte death size and the formation of crown-like structures. The adipocyte death size is reached when the intracellular concentration of LPS initiates pyroptosis. The mechanistic details remain to be elucidated, but the observations indicate that adipocytes are stimulated to cell death by processes that involve LPS from the gut microbiota. There is a complex interplay between the composition of the diet and microbiota. This influences the amount of LPS that is translocated from the gut. In particular, the lipid content of a meal may correlate with the amount of LPS built in to chylomicrons. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ambient air pollution exposure has been associated with childhood asthma, but previous studies have primarily focused on prevalence of asthma and asthma-related outcomes and urban traffic-related exposures. OBJECTIVE: We examined nationwide associations between pre- and postnatal exposure to ambient air pollution components and asthma incidence in children age 0–19 y. METHODS: Asthma incidence was identified from hospital admission, emergency room, and outpatient contacts among all live-born singletons born in Denmark between 1998 and 2016. We linked registry data with monthly mean concentrations of particulate matter (PM) with aerodynamic diameter ≤2.5 μm (PM2.5) and PM with aerodynamic diameter ≤10 μm (PM10), nitrogen dioxide (NO2), nitrogen oxides, elemental carbon, and organic carbon (OC), sulfur dioxide, ozone, sulfate, nitrate, ammonium, secondary organic aerosols, and sea salt. Associations were estimated with Cox proportional hazard models using fixed prenatal exposure means and time-varying postnatal exposures. RESULTS: Of the 1,060,154 children included, 6.1% had asthma during the mean follow-up period of 8.8 y. The risk of asthma increased with increasing prenatal exposure to all pollutants except for O3 and sea salt. We also observed increased risk after restriction to asthma after age 4 y, after additional adjustment for area-specific socioeconomic status, and for postnatal exposure to most pollutants. The hazard ratio (HR) associated with an interquartile range increase of 2.4 and 8.7 µg/m³ in prenatal exposure was 1.06 [95% confidence interval (CI): 1.04, 1.08] for PM2.5 and 1.04 (95% CI: 1.02, 1.05) for NO2, respectively. This association with PM2.5 was stable after adjustment for NO2, whereas it attenuated for NO2 to 1.01 (95% CI: 0.99, 1.03) after adjustment for PM2.5. For a 0.5-µg/m³ increase in prenatal OC exposure, for which biomass is an important source, the HR was 1.08 (95% CI: 1.06, 1.10), irrespective of adjustment for PM2.5. DISCUSSION: These findings suggest that early-life exposure to ambient air pollution from multiple sources contributes to asthma development. [ABSTRACT FROM AUTHOR]

Objective To quantify the number of avoidable annual deaths and associated economic benefits from meeting the World Health Organization (WHO) air quality guidelines for ambient concentrations for fine particulate matter (PM2.5) for Member States of the WHO Western Pacific Region. Methods Using the AirQ+ software, we performed a quantitative health impact assessment comparing country-level PM2.5 concentrations with the 2005 and 2021 air quality guidelines recommended maximum concentrations of 10 and 5 µg/m³, respectively. We obtained PM2.5 data from the WHO Global Health Observatory (latest available year 2016), and population and mortality estimates from the United Nations World Population Prospects database for the latest 5-year period available (2015-2019), which we averaged to 1-year estimates. A risk estimate for all-cause mortality, based on a meta-analysis, was embedded within AirQ+ software. Our economic assessment used World Bank value of a statistical life adjusted to country-specific gross domestic product (latest available year 2014). Findings Data were complete for 21 of 27 Member States. If these countries achieved the 2021 guidelines for PM2.5, an estimated 3.1 million deaths would be avoided annually, which are 0.4 million more deaths avoided than meeting the 2005 guidelines. China would avoid the most deaths per 100 000 population (303 deaths) and Brunei Darussalam the least (5 deaths). The annual economic benefit per capita ranged from 5781 United States dollars (US$) in Singapore to US$ 143 in Solomon Islands. Conclusion Implementing effective measures to reduce PM2.5 emissions would save a substantial number of lives and money across the Region. [ABSTRACT FROM AUTHOR]

Aims/hypothesis It has been suggested that air pollution may increase the risk of type 2 diabetes but data on particulate matter with diameter < 2.5 μm (PM 2.5 ) are inconsistent. We examined the association between long-term exposure to PM 2.5 and diabetes incidence. Methods We used the Danish Nurse Cohort with 28,731 female nurses who at recruitment in 1993 or 1999 reported information on diabetes prevalence and risk factors, and obtained data on incidence of diabetes from National Diabetes Register until 2013. We estimated annual mean concentrations of PM 2.5 , particulate matter with diameter < 10 μm (PM 10 ), nitrogen oxides (NO x ) and nitrogen dioxide (NO 2 ) at their residence since 1990 using a dispersion model and examined the association between the 5-year running mean of pollutants and diabetes incidence using a time-varying Cox regression. Results Of 24,174 nurses 1137 (4.7%) developed diabetes. We detected a significant positive association between PM 2.5 and diabetes incidence (hazard ratio; 95% confidence interval: 1.11; 1.02–1.22 per interquartile range of 3.1 μg/m 3 ), and weaker associations for PM 10 (1.06; 0.98–1.14 per 2.8 μg/m 3 ), NO 2 (1.05; 0.99–1.12 per 7.5 μg/m 3 ), and NO x (1.01; 0.98–1.05 per 10.2 μg/m 3 ) in fully adjusted models. Associations with PM 2.5 persisted in two-pollutant models. Associations with PM 2.5 were significantly enhanced in never smokers (1.24; 1.09–1.42), and augmented in obese (1.25; 1.06–1.47) and subjects with myocardial infarction (1.32; 0.86–2.02), but without significant interaction. Conclusions/interpretation Fine particulate matter may the most relevant pollutant for diabetes development among women, and non-smokers, obese women, and heart disease patients may be most susceptible. [ABSTRACT FROM AUTHOR]

[Display omitted] • We examined the 9th-grade exit exams of 785,312 children in Denmark. • Children's GPA was associated with lifetime exposure to air pollution. • An increase of 5 µg/m3 in PM 2.5 was linked to a one-point decrease in GPA. • The negative associations were noticeable in the mathematics and natural sciences. • Girls and children with non-Danish mothers were susceptible to the association. Recent research suggests a link between air pollution and cognitive development in children, and studies on air pollution and academic achievement are emerging. We conducted a nationwide cohort study in Denmark to explore the associations between lifetime exposure to air pollution and academic performance in 9th grade. The study encompassed 785,312 children born in Denmark between 1989 and 2005, all of whom completed 9th-grade exit examinations. Using linear mixed models with a random intercept for each school, we assessed the relationship between 16 years of exposure to PM 2.5 , PM 10 , and gaseous pollutants and Grade Point Averages (GPA) in exit examinations, covering subjects such as Danish literature, Danish writing, English, mathematics, and natural sciences. The study revealed that a 5 µg/m3 increase in PM 2.5 and PM 10 was associated with a decrease of 0.99 (95 % Confidence Intervals: −1.05, −0.92) and 0.46 (−0.50, −0.41) in GPA, respectively. Notably, these negative associations were more pronounced in mathematics and natural sciences compared to language-related subjects. Additionally, girls and children with non-Danish mothers were found to be particularly susceptible to the adverse effects of air pollution exposure. These results underscore the potential long-term consequences of air pollution on academic achievement, emphasizing the significance of interventions that foster healthier environments for children's cognitive development. [ABSTRACT FROM AUTHOR]

There are substantial inter-laboratory variations in the levels of DNA damage measured by the comet assay. The aim of this study was to investigate whether adherence to a standard comet assay protocol would reduce inter-laboratory variation in reported values of DNA damage. Fourteen laboratories determined the baseline level of DNA strand breaks (SBs)/alkaline labile sites and formamidopyrimidine DNA glycosylase (FPG)-sensitive sites in coded samples of mononuclear blood cells (MNBCs) from healthy volunteers. There were technical problems in seven laboratories in adopting the standard protocol, which were not related to the level of experience. Therefore, the inter-laboratory variation in DNA damage was only analysed using the results from laboratories that had obtained complete data with the standard comet assay protocol. This analysis showed that the differences between reported levels of DNA SBs/alkaline labile sites in MNBCs were not reduced by applying the standard assay protocol as compared with the laboratory’s own protocol. There was large inter-laboratory variation in FPG-sensitive sites by the laboratory-specific protocol and the variation was reduced when the samples were analysed by the standard protocol. The SBs and FPG-sensitive sites were measured in the same experiment, indicating that the large spread in the latter lesions was the main reason for the reduced inter-laboratory variation. However, it remains worrying that half of the participating laboratories obtained poor results using the standard procedure. This study indicates that future comet assay validation trials should take steps to evaluate the implementation of standard procedures in participating laboratories. [ABSTRACT FROM PUBLISHER]

Of the DNA-derived biomarkers of oxidative stress, urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is the most frequently measured. However, there is significant discrepancy between chromatographic and immunoassay approaches, and intratechnique agreement among all available chromatography-based assays and ELISAs is yet to be established. This is a significant obstacle to their use in large molecular epidemiological studies. To evaluate the accuracy of intra/intertechnique and interlaboratory measurements, samples of phosphate buffered saline and urine, spiked with different concentrations of 8-oxoG, together with a series of urine samples from healthy individuals were distributed to ESCULA members. All laboratories received identical samples, including 2 negative controls that contained no added 8-oxodG. Data were returned from 17 laboratories, representing 20 methods, broadly classified as mass spectrometric (MS), electrochemical detection (EC), or enzyme-linked immunosorbant assay (ELISA). Overall, there was good within-technique agreement, with the majority of laboratories' results lying within 1 SD of their consensus mean. However, ELISA showed more within-technique variation than did the chromatographic techniques and, for the urine samples, reported higher values. Bland-Altman plots revealed good agreement between MS and EC methods but concentration-dependent deviation for ELISA. All methods ranked urine samples according to concentration similarly. Creatinine levels are routinely used as a correction factor for urine concentration, and therefore we also conducted an interlaboratory comparison of methods for urinary creatinine determination, in which the vast majority of values lay within 1 SD of the consensus value, irrespective of the analysis procedure. This study reveals greater consensus than previously expected, although concern remains over ELISA. [ABSTRACT FROM AUTHOR]

The comet assay has become a popular method for the assessment of DNA damage in biomonitoring studies and genetic toxicology. However, few studies have addressed the issue of the noted inter-laboratory variability of DNA damage measured by the comet assay. In this study, 12 laboratories analysed the level of DNA damage in monocyte-derived THP-1 cells by either visual classification or computer-aided image analysis of pre-made slides, coded cryopreserved samples of cells and reference standard cells (calibration curve samples). The reference standard samples were irradiated with ionizing radiation (0–10 Gy) and used to construct a calibration curve to calculate the number of lesions per 106 base pair. All laboratories detected dose–response relationships in the coded samples irradiated with ionizing radiation (1.5–7 Gy), but there were overt differences in the level of DNA damage reported by the different laboratories as evidenced by an inter-laboratory coefficient of variation (CV) of 47%. Adjustment of the primary comet assay end points by a calibration curve prepared in each laboratory reduced the CV to 28%, a statistically significant reduction (P < 0.05, Levene's test). A large fraction of the inter-laboratory variation originated from differences in image analysis, whereas the intra-laboratory variation was considerably smaller than the variation between laboratories. In summary, adjustment of primary comet assay results by reference standards reduces inter-laboratory variation in the level of DNA damage measured by the alkaline version of the comet assay. [ABSTRACT FROM PUBLISHER]

Abstract: Objectives: Characteristic for the genes encoding glutathione S-transferase (GST) M1 and GSTT1 is a null allele, suggested to increase susceptibility to chronic diseases. We report an optimized method for the determination of copy number variation (CNV) in GST genes. Design and methods: Real-time multiplex PCR reactions were optimized for quantification of GSTM1 and GSTT1 CNV using the ΔC t method, a fixed volume of diluted DNA, a total volume of 10 μL, 384-well formats, and single determinations of each sample. Results: Consistent genotyping was obtained using DNA in a range of 0.41 ng to 100 ng. In a general population sample of 20,687 individuals the genotype frequencies were concordant with other methods used as standards. Throughput was 4600 genotypes per day at a reagent price of 0.5 euros per sample. Conclusions: This high-throughput, low cost method accurately determines CNV in the GST genes enabling reliable estimates of disease prediction in large epidemiological samples. [Copyright &y& Elsevier]

Abstract: Exposure to ambient air particulate matter (PM) is associated with pulmonary and cardiovascular diseases and cancer. The mechanisms of PM-induced health effects are believed to involve inflammation and oxidative stress. The oxidative stress mediated by PM may arise from direct generation of reactive oxygen species from the surface of particles, soluble compounds such as transition metals or organic compounds, altered function of mitochondria or NADPH-oxidase, and activation of inflammatory cells capable of generating ROS and reactive nitrogen species. Resulting oxidative DNA damage may be implicated in cancer risk and may serve as marker for oxidative stress relevant for other ailments caused by particulate air pollution. There is overwhelming evidence from animal experimental models, cell culture experiments, and cell free systems that exposure to diesel exhaust and diesel exhaust particles causes oxidative DNA damage. Similarly, various preparations of ambient air PM induce oxidative DNA damage in in vitro systems, whereas in vivo studies are scarce. Studies with various model/surrogate particle preparations, such as carbon black, suggest that the surface area is the most important determinant of effect for ultrafine particles (diameter less than 100nm), whereas chemical composition may be more important for larger particles. The knowledge concerning mechanisms of action of PM has prompted the use of markers of oxidative stress and DNA damage for human biomonitoring in relation to ambient air. By means of personal monitoring and biomarkers a few studies have attempted to characterize individual exposure, explore mechanisms and identify significant sources to size fractions of ambient air PM with respect to relevant biological effects. In these studies guanine oxidation in DNA has been correlated with exposure to PM2.5 and ultrafine particles outdoor and indoor. Oxidative stress-induced DNA damage appears to an important mechanism of action of urban particulate air pollution. Related biomarkers and personal monitoring may be useful tools for risk characterization. [Copyright &y& Elsevier]

Air force ground crew personnel are potentially exposed to fuels and lubricants, as raw materials, vapours and combustion exhaust emissions, during operation and maintenance of aircrafts. This study investigated exposure levels and biomarkers of effects for employees at a Danish air force military base. We enrolled self-reported healthy and non-smoking employees (n = 79) and grouped them by exposure based on job function, considered to be potentially exposed (aircraft engineers, crew chiefs, fuel operators and munition specialists) or as reference group with minimal occupational exposure (avionics and office workers). We measured exposure levels to polycyclic aromatic hydrocarbons (PAHs) and organophosphate esters (OPEs) by silicone bands and skin wipes (PAHs only) as well as urinary excretion of PAH metabolites (OH-PAHs). Additionally, we assessed exposure levels of ultrafine particles (UFPs) in the breathing zone for specific job functions. As biomarkers of effect, we assessed lung function, plasma levels of acute phase inflammatory markers, and genetic damage levels in peripheral blood cells. Exposure levels of total PAHs, OPEs and OH-PAHs did not differ between exposure groups or job functions, with low correlations between PAHs in different matrices. Among the measured job functions, the UFP levels were higher for the crew chiefs. The exposure level of the PAH fluorene was significantly higher for the exposed group than the reference group (15.9 ± 23.7 ng/g per 24 h vs 5.28 ± 7.87 ng/g per 24 h, p = 0.007), as was the OPE triphenyl phosphate (305 ± 606 vs 19.7 ± 33.8 ng/g per 24 h, p = 0.011). The OPE tris(1,3-dichlor-2-propyl)phosphate had a higher mean in the exposed group (60.7 ± 135 ng/g per 24 h) compared to the reference group (8.89 ± 15.7 ng/g per 24 h) but did not reach significance. No evidence of effects for biomarkers of systemic inflammation, genetic damage or lung function was found. Overall, our biomonitoring study show limited evidence of occupational exposure of air force ground crew personnel to UFPs, PAHs and OPEs. Furthermore, the OH-PAHs and the assessed biomarkers of early biological effects did not differ between exposed and reference groups. [ABSTRACT FROM AUTHOR]

BACKGROUND: Associations between long-term exposure to air pollution and road traffic noise have been established for ischemic heart disease, but findings have been mixed for atrial fibrillation (AF). OBJECTIVES: The goal of the study was to examine associations of long-term exposure to road traffic noise and air pollution with AF. METHODS: Time-varying Cox regression models were used to estimate associations of 1-, 3-, and 23-y mean road traffic noise and air pollution exposures with AF incidence in 23,528 women enrolled in the Danish Nurse Cohort (age >44y at baseline in 1993 or 1999). AF diagnoses were ascertained via the Danish National Patient Register. Annual mean weighted 24-h average road traffic noise levels (Lden) at the nurses’ residences, since 1970, were estimated using the Nord2000 model, and annual mean levels of particulate matter with a diameter <2.5µm (PM2.5) and nitrogen dioxide (NO2) were estimated using the DEHM/UBM/AirGIS model. RESULTS: Of 23,528 nurses with no prior AF diagnosis at the cohort baseline, 1,522 developed AF during follow-up. In a fully adjusted model (including PM2.5), the estimated risk of AF was 18% higher [hazard ratio (HR); 95% confidence interval (CI): 1.18; 1.02, 1.36] in nurses with residential 3-y mean Lden levels >58?dB vs. <48?dB, with similar findings for 1-y mean exposures. A 3.9-µg/m³ increase in 3-y mean PM2.5 was associated with incident AF before and after adjustment for concurrent exposure to road traffic noise (HR 1.09; 95% CI: 1.00, 1.20 and 1.08; 95% CI: 0.97, 1.19, respectively). Associations with 1-y mean PM2.5 exposures were positive but closer to the null and not significant. Associations with NO2 were null for all time periods before and after adjustment for road traffic noise and inverse when adjusted for concurrent PM2.5. CONCLUSION: Our analysis of prospective data from a cohort of Danish female nurses followed for up to 14 y provided suggestive evidence of independent associations between incident AF and 1- and 3-y exposures to road traffic noise and PM2.5. [ABSTRACT FROM AUTHOR]

The health effects of diesel exhaust particles (DEP) are thought to involve oxidative damage. We have investigated the effect of intratracheal DEP instillation to guinea pigs in three groups of 12 animals each given 0, 0.7, or 2.1 mg. Five days later guinea pigs exposed to DEP had increased levels of oxidized amino acids (γ-glutamyl semialdehyde), DNA strand breaks, and 7-hydro-8-oxo-2′-deoxyguanosine (8-oxodG) in the lung. Bulky DNA ad- ducts were not significantly elevated in the lung. The antioxidant enzyme activity of glutathione reductase was increased in the lung of DEP-exposed guinea pigs, whereas glutathione peroxidase and superoxide dismutase enzyme activities were unaltered. There was no difference in DNA strand breaks in lymphocytes or urinary excretion of 8-oxodG at the two doses tested. Protein oxidations in plasma and in erythrocytes were not altered by DEP exposure. The concentrations of ascorbate in liver, lung, and plasma were unaltered by the DEP exposure. The results indicate that in guinea pigs DEP causes oxidative DNA damage rather than bulky DNA adducts in the lung. Guinea pigs, which are similar to humans with respect to vitamin C metabolism, may serve as a new model for the study of oxidative damage induced by particulate matter. [Copyright &y& Elsevier]

This study was set up to investigate the relationships between the formation and removal of DNA damage in form of 8-oxodeoxyguanosine (8-oxodG) in neonatal (day 16 of gestation) as compared to adult rats. The hypothesis addressed was whether the rapidly dividing foetal tissue has an enhanced requirement of DNA repair providing protection against potentially mutagenic DNA damages such as 8-oxodG. The activity of the primary 8-oxodG-repair protein OGG1 was measured by a DNA incision assay and the expression of OGG1 mRNA was measured by Real-Time PCR normalised to 18S rRNA. The tissue level of 8-oxodG was measured by HPLC-ECD. We found a 2–3-fold increased incision activity in the foetal control tissue, together with a 3–15-fold increase in mRNA of OGG1 as compared to liver tissue from adult rats. The levels of 8-oxodG in the foetal tissue were unaltered as compared to the adult groups. To increase the levels of 8-oxodG, the rats received an injection (i.p.) of the hepatotoxin 2-nitropropane. The compound induced significant levels of 8-oxodG in male rat livers 5 h after the injection and in the foetuses 24 h after the injection, while the female rats showed no increase in 8-oxodG. The incision activity was slightly depressed in both male and female liver tissue and in the foetal tissue 5 h after the injection, but significantly increased from 5 to 24 h after the injection. However, it did not reach levels significantly above the control levels.In conclusion, this study confirms that foetal tissue has increased levels of OGG1 mRNA and correspondingly an enhanced incision activity on an 8-oxodG substrate in a crude tissue extract. [ABSTRACT FROM AUTHOR]

Rapidly proliferating tissue with synthesis of a large number of cellular macromolecules including DNA, may require enhanced DNA repair capacity in order to avoid fixation of promutagenic DNA lesions to mutations. This hypothesis was addressed by assessing the incision activity and the mRNA level of the DNA repair protein rat 8-oxodeoxyguanosine glycosylase (rOGG1) as well as the level of the oxidative stress biomarker 8-oxodeoxyguanosine (8-oxodG) in rat liver tissue before and after partial hepatectomy. A five-fold increase in rOGG1 expression was found at 24 h after PHx relative to the control levels. At 48 h the rOGG1 mRNA levels were reduced to three-times the control values. The corresponding incision activities of rOGG1 in the crude tissue extract as measured by the incision assay were slightly increased both at 24 and 48 h after partial hepatectomy although the changes failed to be statistically significant (P=0.07 and 0.06, respectively). The levels of 8-oxodG were unaltered at 24 h but increased to 1.8 times the control values at 48 h after partial hepatectomy. The study showed that rapid proliferating liver tissue in vivo had an increased expression of the DNA repair protein rOGG1, without significantly increased incision activity on a 8-oxodG-containing substrate and with unchanged levels of 8-oxodG/106 dGuo after 24 h of regeneration. At 48 h the rOGG1 expression was decreased, and the levels of 8-oxodG/106 dGuo increased but still significant changes in the incision activity could not be detected. Thus, we can conclude that the rOGG1 expression is temporarily up-regulated by the proliferating events elicited by partial hepatectomy. [ABSTRACT FROM AUTHOR]

Airway exposure to eg particulate matter is associated with cardiovascular disease including atherosclerosis. Acute phase genes, especially Serum Amyloid A3 (Saa3), are highly expressed in the lung following pulmonary exposure to particles. We aimed to investigate whether the human acute phase protein SAA (a homolog to mouse SAA3) accelerated atherosclerotic plaque progression in Apolipoprotein E knockout (ApoE−/−) mice. Mice were intratracheally (i.t.) instilled with vehicle (phosphate buffered saline) or 2 µg human SAA once a week for 10 weeks. Plaque progression was assessed in the aorta using noninvasive ultrasound imaging of the aorta arch as well as by en face analysis. Additionally, lipid peroxidation, SAA3, and cholesterol were measured in plasma, inflammation was determined in lung, and mRNA levels of the acute phase genes Saa1 and Saa3 were measured in the liver and lung, respectively. Repeated i.t. instillation with SAA caused a significant progression in the atherosclerotic plaques in the aorta (1.5‐fold). Concomitantly, SAA caused a statistically significant increase in neutrophils in bronchoalveolar lavage fluid (625‐fold), in pulmonary Saa3 (196‐fold), in systemic SAA3 (1.8‐fold) and malondialdehyde levels (1.14‐fold), indicating acute phase response (APR), inflammation and oxidative stress. Finally, pulmonary exposure to SAA significantly decreased the plasma levels of very low‐density lipoproteins ‐ low‐density lipoproteins and total cholesterol, possibly due to lipids being sequestered in macrophages or foam cells in the arterial wall. Combined these results indicate the importance of the pulmonary APR and SAA3 for plaque progression. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) aggregates in families and offspring with parental CVD may have adverse risk factor levels long time before the potential onset of CVD. We compared risk factor levels in offspring of parents with atherosclerotic CVD (ASCVD) and parents with no ASCVD at different parental ages at onset. The study included 5751 participants (median age: 50 years) of the Diet, Cancer and Health - Next Generations study. Measurements included blood pressure, body composition and lipid fractions. Information on parental ASCVD and age at disease onset was obtained through register linkage. Parental ASCVD was defined as myocardial infarction, ischemic stroke or peripheral artery disease occurring <70 years, prematurely (mothers: <65 years fathers: <55 years), divided into age categories or using a broader classification of CVD. Linear regression models using Generalized Estimating Equations were used for analysis. Analyses were adjusted for age, sex, education, smoking, alcohol intake, physical activity and some additionally for BMI. Offspring with parental ASCVD had a higher blood pressure, waist circumference, BMI, visceral adipose tissue, percentage of body fat and non-HDL cholesterol levels, but not other lipid levels, compared to offspring with no parental ASCVD (all p < 0.01). Overall, the same patterns were observed for parental ASCVD occurring prematurely and using a broader CVD classification. Offspring with parental ASCVD had a higher blood pressure, higher body composition measures and higher non-HDL cholesterol levels compared to offspring with no parental ASCVD. Findings were overall consistent across different classifications of parental ASCVD. [Display omitted] • Parental ASCVD was associated with more adverse CVD risk factor profiles. • Offspring with parental ASCVD had a higher blood pressure than offspring without. • Body composition measures were higher in offspring with parental ASCVD. • No associations were found for triglycerides, total LDL and HDL cholesterol levels. • Findings were overall consistent for different classifications of parental ASCVD. [ABSTRACT FROM AUTHOR]

BACKGROUND: Air pollution exposure has been linked to coronary heart disease, although evidence on PM[Sub 2.5] and myocardial infarction (MI) incidence is mixed. OBJECTIVES: This prospective cohort study aimed to investigate associations between long-term exposure to air pollution and MI incidence, adjusting for road traffic noise. METHODS: We used data from the nationwide Danish Nurse Cohort on 22,882 female nurses (>44 years of age) who, at recruitment in 1993 or 1999, reported information on cardiovascular disease risk factors. Data on MI incidence was collected from the Danish National Patient Register until the end of 2014. Annual mean concentrations of particulate matter (PM) with a diameter <2.5 µg/m[Sup 3] (PM[Sub 2.5]), PM[Sub 10], nitrogen dioxide (NO[Sub 2]), and nitrogen oxides (NO[Sub x]) at the nurses’ residences since 1990 (PM[Sub 10] and PM[Sub 2.5]) or 1970 (NO[Sub 2] and NO[Sub x]) were estimated using the Danish Eulerian Hemispheric Model/Urban Background Model/AirGIS (DEHM/UBM/AirGIS) dispersion model. We used time-varying Cox regression models to examine the association between 1- and 3-y running means of these pollutants, as well as 23-y running means of NO[Sub 2] and NO[Sub x], with both overall and fatal incident MI. Associations were explored in three progressively adjusted models: Model 1, adjusted for age and baseline year; Model 2, with further adjustment for potential confounding by lifestyle and cardiovascular disease risk factors; and Model 3, with further adjustment for road traffic noise, modeled as the annual mean of a weighted 24-h average (L[Sub den]). RESULTS: Of the 22,882 women, 641 developed MI during a mean follow-up of 18.6 y, 121 (18.9%) of which were fatal. Reported hazard ratios (HRs) were based on interquartile range increases of 5.3, 5.5, 8.1, and 11.5µg/m[Sup 3] for PM[Sub 2.5], PM[Sub 10], NO[Sub 2], and NO[Sub X], respectively. In Model 1, we observed a positive association between a 3-y running mean of PM[Sub 2.5] and an overall incident MI with an HR = 1.20 (95% CI: 1.07, 1.35), which attenuated to HR = 1.06 (95% CI: 0.92, 1.23) in Model 2. In Model 1 for incident fatal MI, we observed a strong association with a 3-y running mean of PM[Sub 2.5], with an HR = 1.69 (95% CI: 1.33, 2.13), which attenuated to HR = 1.35 (95% CI: 1.01, 1.81) in Model 2. Similar associations were seen for PM[Sub 10], with 3-y, Model 2 estimates for overall and fatal incident MI of HR = 1.06 (95% CI: 0.91, 1.23) and HR = 1.35 (95% CI: 1.01, 1.81), respectively. No evidence of an association was observed for NO[Sub 2] or NO[Sub x]. For all pollutants, associations in Model 2 were robust to further adjustment for road traffic noise in Model 3 and were similar for a 1-y running mean exposure. CONCLUSIONS: We found no association between long-term exposure to PM[Sub 2.5], PM[Sub 10], NO[Sub 2], or NO[Sub x] and overall MI incidence, but we observed positive associations for PM[Sub 2.5] and PM[sub 10] with fatal MI. We present novel findings that the association between PM and MI incidence is robust to adjustment for road traffic noise. https://doi.org/10.1289/EHP5818 [ABSTRACT FROM AUTHOR]

• Particles were collected in diesel-powered trains and firefighter training location. • Particles generated intracellular reactive oxygen species in A549 cells. • Long-term exposure to particles promoted shortening in telomeres in A549 cells. • Shorter telomeres were observed in mononuclear blood cells of particle-exposed humans. Particulate matter (PM) from combustion processes has been associated with oxidative stress to DNA, whereas effects related to telomere dysfunction are less investigated. We collected air-borne PM from a passenger cabin of a diesel-propelled train and at a training facility for smoke diving exercises. Effects on oxidative stress biomarkers, genotoxicity measured by the comet assay and telomere length in PM-exposed A549 cells were compared with the genotoxicity and telomere length in peripheral blood mononuclear cells (PBMCs) from human volunteers exposed to the same aerosol source. Although elevated levels of DNA strand breaks and oxidatively damaged DNA in terms of Fpg-sensitive sites were observed in PBMCs from exposed humans, the PM collected at same locations did not cause genotoxicity in the comet assay in A549 cells. Nevertheless, A549 cells displayed telomere length shortening after four weeks exposure to PM. This is in line with slightly shorter telomere length in PBMCs from exposed humans, although it was not statistically significant. In conclusion, the results indicate that genotoxic potency measured by the comet assay of PM in A549 cells may not predict genotoxicity in exposed humans, whereas telomere length measurements may be a novel indicator of genotoxic stress in cell cultures and humans. [ABSTRACT FROM AUTHOR]

Aim: To investigate if ischemic heart disease (IHD) and cerebrovascular disease is associated with long-term occupational exposure to ultrafine particles (UFP) outdoors at an airport.Methods and Results: This is a register-based follow-up study based on a cohort comprising an exposed group of 6515 men employed in unskilled work at Copenhagen Airport and a reference group of 61,617 men in unskilled work in other firms in greater Copenhagen during 1990-2012. The exposure was assessed from information on proportion of time spent on the airport apron for each calendar year (apron-years) and the primary exposure measure was cumulated apron-years. The cohort was merged to the National Patient Register that includes data on all contacts to public and private hospitals in Denmark and the Register of Causes of Death. Risk estimates were provided by Poisson regression and adjusted for age, calendar year and educational level. We found no associations between cumulative apron-years and IHD (IRR, 1.00; 95%CI, 0.97-1.03) or cerebrovascular disease (IRR, 1.00; 0.98-1.02) when adjusted for confounders.Conclusion: In this large cohort study, we found no association between outdoor occupational exposure to UFP and IHD and cerebrovascular disease. [ABSTRACT FROM AUTHOR]

• Oxidatively damaged DNA was measured with the comet assay in blood cells. • Intake of fruit, vegetable, whole grains, fish, salad and potatoes were assessed. • Levels of Fpg-sensitive sites were inversely associated with intake of fish. • Levels of Fpg-sensitive sites were inversely associated with intake of salad. • There was no association between dietary items and DNA repair activity. This study investigated associations between levels of oxidatively damaged DNA, measured by the formamidopyrimidine DNA glycosylase (Fpg)-modified comet assay and intake of fish, salad, fruits, vegetables, wholegrain items, and potatoes in a cross-sectional study of 382 men and 591 women between 18 and 93 years. Intake of dietary items was obtained from questionnaires, and stratified into less than once per week, weekly or daily consumption. Intake of fish as main course was inversely associated with levels of Fpg-sensitive sites in peripheral blood mononuclear cells (PBMCs) in especially women (P < 0.001 multivariate linear regression). Intake of fish was also inversely associated with lower levels of Fpg-sensitive sites in men (P < 0.05, univariate analysis), although it was not statistically significant in analysis adjusted for lifestyle and other dietary factors. Intake of salad was inversely associated with levels of Fpg-sensitive sites in men (P < 0.001, multivariate linear regression). Statistically significant associations were also observed for intake of vegetables and potatoes in men, although these were weak and not robust in all statistical models. The sum the six individual dietary items was inversely associated with levels of Fpg-sensitive sites in the strata of men (P < 0.001, multivariate linear regression). Finally, levels of DNA repair incision activity were not associated with individual food categories or the total dietary food score. In summary, consumption of health-promoting foods is associated with lower levels of Fpg-sensitive sites in human PBMCs and strongest effects in the present population were ingestions of fish and salad. [ABSTRACT FROM AUTHOR]

Vegetable carbon (E153) and titanium dioxide (E171) are widely used as black and white food colour additives. The aim of this study was to assess gastrointestinal tight junction and systemic genotoxic effects in rats following exposure to E153 and E171 for 10 weeks by oral gavage once a week. The expression of tight junction proteins was assessed in intestinal tissues. Levels of DNA strand breaks, oxidatively damaged DNA and telomere length were assessed in secondary organs. Hydrodynamic suspensions of E153 and E173 indicated mean particles sizes of 230 and 270 nm, respectively, and only E153 gave rise to intracellular production of reactive oxygen species in colon epithelial (Caco-2) cells. Rats exposed to E153 (6.4 mg/kg/week) or E171 (500 mg/kg/week) had decreased gene expression of the tight junction protein TJP1 (P < 0.05). E153 (6.4 mg/kg/week) also decreased OCLN (P < 0.05) in the colon and occludin protein expression in the small intestine (P < 0.05). Furthermore, E153 or E171 exposed rats had shorter telomeres in the lung (P < 0.05). Plasma from particle-exposed rats also produced telomere shortening in cultured lung epithelial cells. There were unaltered levels of oxidatively damaged DNA in the liver and lung and no changes in the DNA repair activity of oxidatively damaged DNA in the lung. Altogether, these results indicate that intragastric exposure to E153 and E171 is associated with reduced tight junction protein expression in the intestinal barrier and telomere length shortening in the lung in rats. [ABSTRACT FROM AUTHOR]

Abstract Background Health impact assessment (HIA) of exposure to air pollution is commonly based on city level (fine) particle concentration and may underestimate health consequences of changing local traffic. Exposure to traffic-related air pollution can be assessed at a high resolution by modelling levels of nitrogen dioxide (NO 2), which together with ultrafine particles mainly originate from diesel-powered vehicles in urban areas. The purpose of this study was to estimate the health benefits of reduced exposure to vehicle emissions assessed as NO 2 at the residence among the citizens of Copenhagen Municipality, Denmark. Methods We utilized residential NO 2 concentrations modelled by use of chemistry transport models to calculate contributions from emission sources to air pollution. The DYNAMO-HIA model was applied to the population of Copenhagen Municipality by using NO 2 concentration estimates combined with demographic data and data from nationwide registers on incidence and prevalence of selected diseases, cause specific mortality, and total mortality of the population of Copenhagen. We used exposure-response functions linking NO 2 concentration estimates at the residential address with the risk of diabetes, cardiovascular diseases, and respiratory diseases derived from a large Danish cohort study with the majority of subjects residing in Copenhagen between 1971 and 2010. Different scenarios were modelled to estimate the dynamic impact of NO 2 exposure on related diseases and the potential health benefits of lowering the NO 2 level in the Copenhagen Municipality. Results The annual mean NO 2 concentration was 19.6 μg/m3 and for 70% of the population the range of exposure was between 15 and 21 μg/m3. If NO 2 exposure was reduced to the annual mean rural level of 6 μg/m3, life expectancy in 2040 would increase by one year. The greatest gain in disease-free life expectancy would be lifetime without ischemic heart disease (1.4 years), chronic obstructive pulmonary disease (1.5 years for men and 1.6 years for women), and asthma (1.3 years for men and 1.5 years for women). Lowering NO 2 exposure by 20% would increase disease-free life expectancy for the different diseases by 0.3–0.5 years. Using gender specific relative risks affected the results. Conclusions Reducing the NO 2 exposure by controlling traffic-related air pollution reduces the occurrence of some of the most prevalent chronic diseases and increases life expectancy. Such health benefits can be quantified by DYNAMO-HIA in a high resolution exposure modelling. This paper demonstrates how traffic planners can assess health benefits from reduced levels of traffic-related air pollution. Highlights • Nitrogen oxide concentration can serve as a proxy of exposure to traffic-related air pollution. • The annual mean nitrogen oxide concentration is 19.6 μg/m3 in Copenhagen. • One-year gain in life expectancy by lowering nitrogen oxide exposure to rural level • Marked increase in disease-free life expectancies by reducing nitrogen oxide exposure [ABSTRACT FROM AUTHOR]

Abstract Animal studies have shown that titanium dioxide (TiO 2) exposure affects arterial vasomotor function, whereas little is known about the effects in arteries from humans. This study investigated vasomotor responses after direct exposure of human subcutaneous arteries to food-grade TiO 2 (E171) (14 or 140 μg/ml) for 30 min and 18 h. Vasomotor responses to bradykinin, 5-hydroxytryptamine (5-HT), sarafotoxin 6c (S6c) and nitroglycerin were recorded in wire-myographs. Vasoconstrictor responses to 5-HT were increased in arteries exposed to E171 for 18 h (P < 0.05). Furthermore, an increase in S6c responses was seen in low concentration E171 exposed arteries (30 min exposure; P < 0.05). The vasorelaxation response to nitroglycerin was increased in low concentration E171 exposed arteries (30 min exposure; P < 0.05). Vasorelaxation responses to bradykinin were unaffected after treatment with E171. There was no difference in gene expression levels of intercellular cell adhesion molecule 1, vascular cell adhesion molecule 1, 5-hydroxytryptamine receptor 1B, 5-hydroxytryptamine receptor 2A, endothelin receptor A and endothelin receptor B in E171 exposed arteries after exposure to TiO 2 for 30 min or 18 h. In conclusion, this study shows that the same type of vasomotor dysfunction is found in artery segments of rats and humans following ex vivo exposure to E171. Highlights • Exposure of human arteries to E171 resulted in increased vasocontraction response. • There were unaltered expressions of 5-hydroxytryptamine or sarafotoxin 6c receptors. • The exposure did not change the expression of cell adhesion molecules in arteries. • Exposure to E171 increased the endothelial-independent vasorelaxation response. [ABSTRACT FROM AUTHOR]

Fine particulate matter (PM 2.5) is a well-recognized risk factor for premature death. However, evidence on which PM 2.5 components are most relevant is unclear. We evaluated the associations between mortality and long-term exposure to eight PM 2.5 elemental components [copper (Cu), iron (Fe), zinc (Zn), sulfur (S), nickel (Ni), vanadium (V), silicon (Si), and potassium (K)]. Studied outcomes included death from diabetes, chronic kidney disease (CKD), dementia, and psychiatric disorders as well as all-natural causes, cardiovascular disease (CVD), respiratory diseases (RD), and lung cancer. We followed all residents in Denmark (aged ≥30 years) from January 1, 2000 to December 31, 2017. We used European-wide land-use regression models at a 100 × 100 m scale to estimate the residential annual mean levels of exposure to PM 2.5 components. The models were developed with supervised linear regression (SLR) and random forest (RF). The associations were evaluated by Cox proportional hazard models adjusting for individual- and area-level socioeconomic factors and total PM 2.5 mass. Of 3,081,244 individuals, we observed 803,373 death from natural causes during follow-up. We found significant positive associations between all-natural mortality with Si and K from both exposure modeling approaches (hazard ratios; 95% confidence intervals per interquartile range increase): SLR-Si (1.04; 1.03–1.05), RF-Si (1.01; 1.00–1.02), SLR-K (1.03; 1.02–1.04), and RF-K (1.06; 1.05–1.07). Strong associations of K and Si were detected with most causes of mortality except CKD and K, and diabetes and Si (the strongest associations for psychiatric disorders mortality). In addition, Fe was relevant for mortality from RD, lung cancer, CKD, and psychiatric disorders; Zn with mortality from CKD, RD, and lung cancer, and; Ni and V with lung cancer mortality. We present novel results of the relevance of different PM 2.5 components for different causes of death, with K and Si seeming to be most consistently associated with mortality in Denmark. • Fine particulate matter (PM 2.5) is linked to premature mortality. • Researches on which PM 2.5 components are more responsible is limited. • With 3 million Danes, we studied how PM 2.5 elemental components links with mortality. • Potassium and silicon were the most relevant PM 2.5 components with mortality. • Different PM 2.5 components were associated with different mortality outcomes. [ABSTRACT FROM AUTHOR]

Ambient air pollution including ozone and especially particulate matter represents important causes of cardiovascular disease. However, there is limited knowledge on indoor air dust with respect to this risk and the potential interactions between dust and ozone. Here, we exposed 23 healthy elderly subjects for 5.5 h, to either clean air, house dust at 275 µg/m³ (diameter < 2.5 µm), ozone at 100 ppb or combined house dust and ozone in a double-blinded randomized cross-over study. The combined house dust and ozone exposure was associated with a 48% (95% CI 24%-65%) decrease as compared with the clean air exposure, in CD34+KDR+ late endothelial progenitor cells (EPCs) per leukocyte in the blood shortly after exposure, whereas none of the single exposures resulted in a significant effect. The combined exposure also increased reactive oxygen species production capacity in granulocytes and monocytes as well as an up-regulation of interleukin-8 mRNA levels in leukocytes. Ozone alone reduced the gene expression of tumor necrosis factor and C-C motif chemokine ligand 2, while dust alone showed no effects. The combined exposure to house dust and ozone also reduced levels of oxidized purines in DNA consistent with concomitant up-regulation of mRNA of the repair enzyme 8-oxoguanine DNA glycosylase. The reduction in late EPCs can be an indicator of cardiovascular risk caused by the combination of pulmonary oxidative stress induced by ozone and the inflammatory potential of the house dust. These data were corroborated with in vitro findings from exposed human macrophages and endothelial cells. [ABSTRACT FROM AUTHOR]

Particles from burning candles contribute to the overall indoor exposure to particulate matter (PM). However, little is known about the effects of indoor sources of particles on cardiovascular disease endpoints. This study investigated the effect of pulmonary exposure to particles from combustion of candles and progression of atherosclerosis. Telomere shortening was assessed in tissues due to its relationship to risk of cardiovascular diseases. The particles were collected from burning candles and used for toxicological studies in cultured endothelial cells and apolipoprotein E (ApoE) knockout mice. Three hours exposure to particles increased the production of reactive oxygen species in endothelial cells, whereas there was no effect on cytotoxicity. Intratracheal instillation of particles (0.5 or 5 mg/kg) once a week for 5 weeks in ApoE −/− mice was associated with an accelerated progression of atherosclerosis in aorta and telomere shortening in the lung and spleen, whereas there was no effect on inflammation in the lungs (i.e. cell numbers), cell damage (i.e. lactate dehydrogenase) and lung barrier damage (i.e. protein concentration) as measured in bronchoalveolar lavage fluid. The results indicate that particles from burning candles are hazardous and this indoor emission source is an important contribution to the health risk of exposure to PM. [ABSTRACT FROM AUTHOR]