Indoor air pollution exposure and early childhood development in the Upstate KIDS Study.

BACKGROUND: Limited human studies have investigated the impact of indoor air pollution on early childhood neurodevelopment among the US population. We aimed to examine the associations between prenatal and postnatal indoor air pollution exposure and early childhood development in a population-based birth cohort. METHODS: This analysis included 4735 mother-child pairs enrolled between 2008 and 2010 in the Upstate KIDS Study. Indoor air pollution exposure from cooking fuels, heating fuels, and passive smoke during pregnancy, and at 12 and 36 months after birth were assessed by questionnaires. Five domains of child development were assessed by the Ages and Stages Questionnaire at 4, 8, 12, 18, 24, 30, and 36 months. Generalized estimating equations were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for potential confounders. RESULTS: Exposure to unclean cooking fuels (natural gas, propane, or wood) throughout the study period was associated with increased odds of failing any development domain (OR = 1.28, 95% CI 1.07, 1.53), the gross motor domain (OR = 1.52, 95% CI: 1.09, 2.13), and the personal-social domain (OR = 1.36, 95% CI: 1.00, 1.85), respectively. Passive smoke exposure throughout the study period increased the odds of failing the problem-solving domain by 71% (OR = 1.71, 95% CI 1.01, 2.91) among children of non-smoking mothers. No association was found between heating fuel use and failing any or specific domains. CONCLUSION: Unclean cooking fuel use and passive smoke exposure during pregnancy and early life were associated with developmental delays in this large prospective birth cohort.

Evaluating how occupational exposure to organophosphates and pyrethroids impacts ADHD severity in Egyptian male adolescents.

BACKGROUND: Attention Deficit/Hyperactivity Disorder (ADHD) is a neurodevelopmental disorder characterized by deficits in attention and hyperactivity/impulsivity that cause impairments to daily living. An area of long-standing concern is understanding links between environmental toxicants, including pesticides, and the development or worsening of ADHD. OBJECTIVES: The present study evaluated associations between occupational pesticide exposure, specifically organophosphate (OP) pesticides, chlorpyrifos (CPF) and the pyrethroids (PYR) alpha-cypermethrin (αCM) and lambda-cyhalothrin (λCH), and symptoms of ADHD in a longitudinal study among Egyptian adolescent males. METHODS: Participants (N = 226, mean age = 17) were Egyptian adolescent males who either applied pesticides or were non-applicators. Urinary trichloro-2-pyridinol (TCPy) was measured as a specific metabolite biomarker of exposure to chlorpyrifos. Urinary 3-phenoxybenzoic acid (3-PBA) was measured as a general metabolite biomarker of exposure to pyrethroids, while urinary cis-3-(2,2- dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid (cis-DCCA) was measured as a specific biomarker of exposure to αCM and lambda cyhalothric acid (λCH acid) measured as a specific biomarker of exposure to λCH. Ordinal logistic regression models controlling for age were used to determine the likelihood of ADHD development (measured via parent-reported ADHD symptoms) as the level of biomarkers of pesticide exposure increased. RESULTS: Cis-DCCA was the only biomarker associated with higher likelihood ADHD symptoms (> 0.60 vs. 0-0.17 µg/g creatinine; OR = 2.82, 95% CI: 1.29-6.14). All participants reported clinical levels of ADHD symptoms when compared to national norms used in the United States. TCPy, trans-DCCA and λCH acid were not associated with risk of ADHD symptoms after controlling for levels of cis-DCCA. No other metabolites were associated with the number of ADHD symptoms. There were no interaction effects found for exposure to both OPs and Pyrethroids. DISCUSSION: The results suggest that exposure to the pyrethroid αCM is associated with more ADHD symptoms. Methodological and cultural considerations in need of further study are discussed.

Effects of exposure to environmental pollutants on mitochondrial DNA copy number: a meta-analysis.

Exposure to environmental pollutants has been associated with alteration on relative levels of mitochondrial DNA copy number (mtDNAcn). However, the results obtained from epidemiological studies are inconsistent. This meta-analysis aimed to evaluate whether environmental pollutant exposure can modify the relative levels of mtDNAcn in humans. We performed a literature search using PubMed, Scopus, and Web of Science databases. We selected and reviewed original articles performed in humans that analyzed the relationship between environmental pollutant exposure and the relative levels of mtDNAcn; the selection of the included studies was based on inclusion and exclusion criteria. Only twenty-two studies fulfilled our inclusion criteria. A total of 6011 study participants were included in this systematic review and meta-analysis. We grouped the included studies into four main categories according to the type of environmental pollutant: (1) heavy metals, (2) polycyclic aromatic hydrocarbons (PAHs), (3) particulate matter (PM), and (4) cigarette smoking. Inconclusive results were observed in all categories; the pooled analysis shows a marginal increase of relative levels of mtDNAcn in response to environmental pollutant exposure. The trial sequential analysis and rate confidence in body evidence showed the need to perform new studies. Therefore, a large-scale cohort and mechanistic studies in this area are required to probe the possible use of relative levels of mtDNAcn as biomarkers linked to environmental pollution exposure.

Acute and Cumulative Effects of Repeated Exposure to Chlorpyrifos on the Liver and Kidney Function among Egyptian Adolescents.

BACKGROUND: There is a paucity of research that tracks changes in liver and kidney function among pesticide applicators. The aim of the current study was to investigate the role of repeated seasonal exposure to the organophosphorus pesticide, chlorpyrifos, on serum measures of liver and kidney function. METHODS: Pesticide exposure was assessed by measuring the urinary concentrations of 3,5,6-trichloro-2 pyridinol (TCPy), a specific biomarker for chlorpyrifos. Chlorpyrifos exposure and 8 serum markers of liver and kidney function were measured at 15 timepoints over 3 years prior to, during, and following the end of seasonal pesticide application among adolescent applicators and non-applicators from 4 field stations in Menoufia, Egypt. RESULTS: Urinary TCPy levels showed increases during the application cycles and recovery at the end of each application season. Altered serum markers of liver and kidney function were associated with chlorpyrifos exposure, with some markers recovering 3 months after the end of exposure each year, while other measures demonstrated progressive increase up to 300% the baseline levels at the end of 3 years. CONCLUSION: The study demonstrated that frequent assessment of liver and kidney function is a sound practice to evaluate cellular injury following chronic repeated occupational and environmental exposure to chlorpyrifos.

Changes in arachidonic acid (AA)- and linoleic acid (LA)-derived hydroxy metabolites and their interplay with inflammatory biomarkers in response to drastic changes in air pollution exposure.

BACKGROUND: Untargeted metabolomics analyses have indicated that fatty acids and their hydroxy derivatives may be important metabolites in the mechanism through which air pollution potentiates diseases. This study aimed to use targeted analysis to investigate how metabolites in arachidonic acid (AA) and linoleic acid (LA) pathways respond to short-term changes in air pollution exposure. We further explored how they might interact with markers of antioxidant enzymes and systemic inflammation. METHODS: This study included a subset of participants (n = 53) from the Beijing Olympics Air Pollution (BoaP) study in which blood samples were collected before, during, and after the Beijing Olympics. Hydroxy fatty acids were measured by liquid chromatography/mass spectrometry (LC/MS). Native total fatty acids were measured as fatty acid methyl esters (FAMEs) using gas chromatography. A set of chemokines were measured by ELISA-based chemiluminescent assay and antioxidant enzyme activities were analyzed by kinetic enzyme assays. Changes in levels of metabolites over the three time points were examined using linear mixed-effects models, adjusting for age, sex, body mass index (BMI), and smoking status. Pearson correlation and repeated measures correlation coefficients were calculated to explore the relationships of metabolites with levels of serum chemokines and antioxidant enzymes. RESULTS: 12-hydroxyeicosatetraenoic acid (12-HETE) decreased by 50.5% (95% CI: -66.5, -34.5; p < 0.0001) when air pollution dropped during the Olympics and increased by 119.4% (95% CI: 36.4, 202.3; p < 0.0001) when air pollution returned to high levels after the Olympics. In contrast, 13-hydroxyoctadecadienoic acid (13-HODE) elevated significantly (p = 0.023) during the Olympics and decreased nonsignificantly after the games (p = 0.104). Interleukin 8 (IL-8) correlated with 12-HETE (r = 0.399, BH-adjusted p = 0.004) and 13-HODE (r = 0.342, BH-adjusted p = 0.014) over the three points; it presented a positive and moderate correlation with 12-HETE during the Olympics (r = 0.583, BH-adjusted p = 0.002) and with 13-HODE before the Olympics (r = 0.543, BH-adjusted p = 0.008). CONCLUSION: AA- and LA-derived hydroxy metabolites are associated with air pollution and might interact with systemic inflammation in response to air pollution exposure.

Evaluation of occupational pesticide exposure on Egyptian male adolescent cognitive and motor functioning.

BACKGROUND: Chronic low-level exposure to organophosphorus pesticides is associated with adverse health effects, including a decline in neurological functioning and long-term impairment. These negative effects may be more detrimental in children and adolescents due to their critical stage in development. Little work has investigated the effects of chronic exposure to pesticides, specifically chlorpyrifos (CPF) during the adolescent period. OBJECTIVES: To examine effects of CPF exposure over a year-long period within a group of male adolescents in Egypt (N = 242, mean age = 17.36), including both pesticide applicators and non-applicators. METHODS: Associations between average CPF exposure (measured via urinary metabolite levels of 3,5,6-trichloro-2-pyridinol [TCPy]) and neurobehavioral functioning were examined in a 1-year longitudinal study. Given previous literature, higher levels of TCPy were expected to be associated with worse neurobehavioral functioning. RESULTS: Using mixed effects linear regression, average TCPy exposure predicted deficits in more complex neurobehavioral tasks (Benton visual retention, digit span reverse, match to sample, serial digit learning, and alternating tapping) with estimates of effects ranging from -0.049 to 0.031. Age (effects ranging from 0.033 to 0.090) and field station (effects ranging from -1.266 to -0.278) were significantly predictive of neurobehavioral functioning over time. An interaction effect was found for field station and TCPy across several neurobehavioral domains. DISCUSSION: Results show that occupational exposure to pesticides may have particularly deleterious effects on complex neurobehavioral domains. Additionally, differences across field stations and the age at which individuals are exposed may be important factors to investigate in future research.

Effect of exposure to 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) on mitochondrial DNA (mtDNA) copy number in rats.

Mitochondria are intracellular organelles responsible for biological oxidation and energy production. These organelles are susceptible to damage from oxidative stress and compensate for damage by increasing the number of copies of their own genome, mitochondrial DNA (mtDNA). Cancer and environmental exposure to some pollutants have also been associated with altered mtDNA copy number. Since exposures to polychlorinated biphenyls (PCBs) and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) have been shown to increase oxidative stress, we hypothesize that mtDNA copy number will be altered with exposure to these compounds. mtDNA copy number was measured in DNA from archived frozen liver and lung specimens from the National Toxicology Program (NTP) study of female Harlan Sprague Dawley rats exposed to TCDD (3, 10, or 100 ng/kg/day), dioxin-like (DL) PCB 126 (10, 100, or 1000 ng/kg/day), non-DL PCB 153 (10, 100, or 1000 µg/kg/day), and PCB 126 + PCB 153 (10 ng/kg/day + 10 µg/kg/day, 100 ng/kg/day + 100 µg/kg/day, or 1000 ng/kg/day + 1000 µg/kg/day, respectively) for 13 and 52 weeks. An increase in mtDNA copy number was observed in the liver and lung of rats exposed to TCDD and the lung of rats exposed to the mixture of PCB 126 and PCB 153. A statistically significant positive dose-dependent trend was also observed in the lung of rats exposed to PCB 126 and a mixture of PCB 153 and PCB 126, although in neither case was the control copy number significantly exceeded at any dose level. These exposures produced a range of pathological responses in these organs in the two-year NTP studies. Conversely, there was a significant decrease or no change in mtDNA copy number in the liver and lung of rats exposed to non-DL PCB 153. This is consistent with a general lack of PCB 153 mediated liver or lung injury in the NTP study, with the exception of liver hypertrophy. Together, the results suggest that an increase in mtDNA copy number may serve as a sensitive, early biomarker of mitochondrial injury and oxidative stress that contributes to the development of the toxicity of dioxin-like compounds.

Telomeres as targets for the toxicity of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and polychlorinated biphenyls (PCBs) in rats.

Telomere length (TL) can be affected by various factors, including age and oxidative stress. Changes in TL have been associated with chronic disease, including a higher risk for several types of cancer. Environmental exposure of humans to PCBs and dioxins has been associated with longer or shorter leukocyte TL. Relative telomere length (RTL) may serve as a biomarker associated with neoplastic and/or non-neoplastic responses observed with chronic exposures to TCDD and PCBs. RTL was measured in DNA isolated from archived frozen liver and lung tissues from the National Toxicology Program (NTP) studies conducted in female Harlan Sprague Dawley rats exposed for 13, 30, and 52 weeks to TCDD, dioxin-like (DL) PCB 126, non-DL PCB 153, and a mixture of PCB 126 and PCB 153. RTL was assessed by quantitative polymerase chain reaction (qPCR). Consistent with literature, decreased liver and lung RTL was seen with aging. Relative to time-matched vehicle controls, RTL was increased in both the liver and lung tissues of rats exposed to TCDD, PCB 126, PCB 153, and the mixture of PCB 126 and PCB 153, which is consistent with most epidemiological studies that found PCB exposures were associated with increased leukocyte RTL. Increased RTL was observed at doses and/or time points where little to no pathology was observed. In addition to serving as a biomarker of exposure to these compounds in rats and humans, increases in RTL may be an early indicator of neoplastic and non-neoplastic responses that occur following chronic exposure to TCDD and PCBs.

Risk perception and behavior in Egyptian adolescent pesticide applicators: an intervention study.

BACKGROUND: Adolescents are engaged in agricultural work, including pesticide application, around the world. Adolescent pesticide applicators are more likely to be exposed to pesticides than their adult counterparts because of their application practice and hygiene habits surrounding pesticide use. There is a need for low-cost interventions to reduce pesticide exposure. We evaluated a theoretically-based educational intervention to change perceptions about the risk of pesticide use and hygiene habits during and after pesticide application for adolescent and young adult pesticide applicators in Egypt. METHODS: Young adult and adolescent male pesticide applicators were given a one-hour educational intervention to inform them about the risk of pesticide use and how to reduce pesticide exposure. The median age of participants was 18 years old. Changes in perceived susceptibility and effectiveness were measured with a survey pre and post-intervention (n = 119) on the same day. The same survey (n = 95) was given 8-months post-intervention to identify sustained effects. Observational checklists of pesticide application practice were also completed during application seasons before and after the intervention. RESULTS: There was an increase in the proportion of individuals who viewed pesticides as being a long-term health risk (74.7% pre-intervention to 97.9% post-intervention, McNemar test p < 0.001). This change remained significant when surveyed at the 8-month follow-up (90.5%, p < 0.001). There was also a sustained improvement regarding participants' views of proper hygiene practice surrounding pesticide application. Applicators were observed wearing goggles, shoes, and masks more frequently post-intervention. CONCLUSION: This theoretically-based intervention is an example of a low-cost solution that can improve adolescents' and young adults' practices regarding pesticide application and personal hygiene practices during and after pesticide application. The intervention can be applied in other countries with similar safety culture surrounding pesticide application.

Responses of serum chemokines to dramatic changes of air pollution levels, a panel study.

Background: Despite the in vitro and in vivo evidence, studies are limited in evaluating whether chemokines are potential inflammatory mediators in response to air pollution exposure in humans. Methods: We conducted a panel study coinciding with the Beijing Olympics, when temporary air pollution controls were implemented. We measured a suite of serum chemokines among healthy adults before, during and after the Olympics, respectively. Linear mixed-effect models were used to evaluate changes in chemokine levels over the three time periods. Results: In response to the 50% drop in air pollution levels during the games, levels of RANTES, MCP-2, and TARC decreased by 25.8%, 20.9% and 35.3%, respectively (p < 0.001) from pre-Olympics, and then increased by 45.8%, 34.9% and 61.5%, respectively (p < 0.001) after the games when air pollution levels went up again. Similar patterns were observed in subgroup analyses by sex, age, smoking and body mass index. GRO-α and IL-8 decreased significantly during the games (22.5% and 30.4%), and increased non-significantly after the games. Eotaxin-1 only increased significantly from during- to post-games. Conclusions: The strongest associations with air pollution levels were observed among RANTES, TARC and MCP-2. Those chemokines may play important roles in the air pollution-induced inflammatory pathway.

Occupational pesticide exposure and symptoms of attention deficit hyperactivity disorder in adolescent pesticide applicators in Egypt.

BACKGROUND: Exposure to environmental chemicals, including organophosphorus pesticides, is associated with behavioral disorders such as attention deficit hyperactivity disorder (ADHD). However, the impact of occupational pesticide exposure on ADHD development in adolescents has not been examined. OBJECTIVE: We examined the association between exposure to chlorpyrifos and ADHD symptoms among adolescents in Egypt. METHODS: Adolescent pesticide applicators and non-applicators, 12-21 years old, participated in a 10-month longitudinal study examining health effects from pesticide exposure. Repeated urine and blood samples were collected at various time points during the 10-months to assess biomarkers of chlorpyrifos exposure (urinary trichloro-2-pyridinol or TCPy) and effect (blood acetyl cholinesterase activity and butyryl cholinesterase activity). Parents from a subset of the cohort (N = 64) completed the Short Form of Conners' Parent Rating Scale - Revised. Poisson regressions were used to examine the associations between the number of ADHD symptoms and occupation and biomarkers. RESULTS: Pesticide applicators had significantly more symptoms of ADHD than participants in the non-applicator group. Urinary TCPy levels were associated with increased symptoms, demonstrating a dose-response effect. Applicators with ADHD reported applying pesticides for more hours during the application season and had greater cumulative TCPy levels than participants without ADHD. One fourth of all applicators met the criteria for an ADHD diagnosis (having 6 or more reported symptoms). CONCLUSIONS: This study provides preliminary evidence of an association between occupational exposure to chlorpyrifos and ADHD symptoms among adolescent pesticide applicators in spite of its limited small sample size. There is a critical need to investigate the susceptibility of children and adolescents to repeated occupational and environmental exposures to pesticides because the developing brain may be uniquely sensitive to the neurotoxic effects of these agents.

Metabolomics Profiling before, during, and after the Beijing Olympics: A Panel Study of Within-Individual Differences during Periods of High and Low Air Pollution.

BACKGROUND: The metabolome is a collection of exogenous chemicals and metabolites from cellular processes that may reflect the body's response to environmental exposures. Studies of air pollution and metabolomics are limited. OBJECTIVES: To explore changes in the human metabolome before, during, and after the 2008 Beijing Olympics Games, when air pollution was high, low, and high, respectively. METHODS: Serum samples were collected before, during, and after the Olympics from 26 participants in an existing panel study. Gas and ultra-high performance liquid chromatography/mass spectrometry were used in metabolomics analysis. Repeated measures ANOVA, network analysis, and enrichment analysis methods were employed to identify metabolites and classes associated with air pollution changes. RESULTS: A total of 886 molecules were measured in our metabolomics analysis. Network partitioning identified four modules with 65 known metabolites that significantly changed across the three time points. All known molecules in the first module ([Formula: see text]) were lipids (e.g., eicosapentaenoic acid, stearic acid). The second module consisted primarily of dipeptides ([Formula: see text], e.g., isoleucylglycine) plus 8 metabolites from four other classes (e.g., hypoxanthine, 12-hydroxyeicosatetraenoic acid). Most of the metabolites in Modules 3 (19 of 23) and 4 (5 of 5) were unknown. Enrichment analysis of module-identified metabolites indicted significantly overrepresented pathways, including long- and medium-chain fatty acids, polyunsaturated fatty acids (n3 and n6), eicosanoids, lysolipid, dipeptides, fatty acid metabolism, and purine metabolism [(hypo) xanthine/inosine-containing pathways]. CONCLUSIONS: We identified two major metabolic signatures: one consisting of lipids, and a second that included dipeptides, polyunsaturated fatty acids, taurine, and xanthine. Metabolites in both groups decreased during the 2008 Beijing Olympics, when air pollution was low, and increased after the Olympics, when air pollution returned to normal (high) levels. https://doi.org/10.1289/EHP3705.

Active and secondhand smoke exposure throughout life and DNA methylation in breast tumors.

PURPOSE: Tobacco smoke exposure has been associated with altered DNA methylation. However, there is a paucity of information regarding tobacco smoke exposure and DNA methylation of breast tumors. METHODS: We conducted a case-only analysis using breast tumor tissue from 493 postmenopausal and 225 premenopausal cases in the Western New York Exposures and Breast Cancer (WEB) study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A, CCND2, BRCA1, FHIT, and SYK) was measured with pyrosequencing. Participants reported their secondhand smoke (SHS) and active smoking exposure for seven time periods. Unconditional logistic regression was used to estimate odds ratios (OR) of having methylation higher than the median. RESULTS: SHS exposure was associated with tumor DNA methylation among postmenopausal but not premenopausal women. Active smoking at certain ages was associated with increased methylation of GSTP1, FHIT, and CDKN2A and decreased methylation of SCGB3A1 and BRCA1 among both pre- and postmenopausal women. CONCLUSION: Exposure to tobacco smoke may contribute to breast carcinogenesis via alterations in DNA methylation. Further studies in a larger panel of genes are warranted.

Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk.

BACKGROUND: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. METHODS: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. RESULTS: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. CONCLUSIONS: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

Ambient air pollution and lung cancer risk among never-smokers in the Women's Health Initiative.

BACKGROUND: Ambient air pollution is classified as a human carcinogen by the International Agency for Research on Cancer (IARC). However, epidemiologic studies supporting this classification have focused on lung cancer mortality rather than incidence, and spatial and temporal resolutions of exposure estimates have varied considerably across studies. METHODS: We evaluated the association of outdoor air pollution and lung cancer incidence among never-smoking participants of the Women's Health Initiative (WHI) study, a large, US-based cohort of postmenopausal women (N = 65,419; 265 cases). We used geospatial models to estimate exposures to fine particulate matter (PM2.5) and nitrogen dioxide (NO2) based on residential addresses at baseline and throughout follow-up. We also characterized exposures to traffic-related air pollution by proximity to major roadways. We estimated hazard ratios (HRs) for the risk of lung cancer in association with these exposure metrics using Cox proportional hazards regression models. RESULTS: No compelling associations of PM2.5 and NO2 exposures with lung cancer risk were observed. An increased risk of lung cancer was observed when comparing those individuals with residences <50 versus ≥200 meters from a primary limited access highway (HR = 5.23; 95% confidence interval = 1.94, 14.13). CONCLUSIONS: Our results do not exclude lung cancer risk estimates observed in association with PM2.5 and NO2 exposures identified in previous studies. Our results suggest that residential proximity to major roadways may be a proxy for carcinogenic exposures not correlated with PM2.5 or NO2 levels. New studies of air pollution and lung cancer incidence should characterize additional aspects of proximity to major roadways.

How do glutathione antioxidant enzymes and total antioxidant status respond to air pollution exposure?

This study aims to investigate how antioxidant enzyme activity and overall antioxidant capacity respond to short-term changes in exposure to air pollution. 201 participants were recruited before- and followed up during- and after- the 2008 Beijing Olympics. Serum levels of antioxidant enzymes including glutathione S-transferases (GST), glutathione peroxidase (GPx), glutathione reductase (GR), and total antioxidant status (TAS) were measured. We used linear mixed-effects models to compare changes in antioxidant enzymes across the three periods after adjusting for potential confounding factors. Among all participants, glutathione peroxidase (GPx) levels decreased by 12.0% when air pollution dropped by 50-60% during the Olympics and increased by 6.5% when air pollution levels rose after the Olympics. The magnitude of increase among males, smokers, and older individuals was relatively smaller compared to females, nonsmokers, and younger individuals. Among all participants, total antioxidant status (TAS) significantly decreased by 6.23% during the games and continued to decrease by 4.41% after the games. However, among females, nonsmokers, and younger participants, there was an increase in TAS response to the elevated air pollution levels. Our study observed strong responses in GPx and TAS levels to the short-term decrease and increase of air pollution levels and responses varied among subgroups.

Lifetime exposure to ambient air pollution and methylation of tumor suppressor genes in breast tumors.

BACKGROUND: We previously reported increased risk of breast cancer associated with early life exposure to two measures of air pollution exposure, total suspended particulates (TSP) and traffic emissions (TE), possible proxies for exposure to polycyclic aromatic hydrocarbons (PAHs). Exposure to PAHs has been shown to be associated with aberrant patterns of DNA methylation in peripheral blood of healthy individuals. Exposure to PAHs and methylation in breast tumor tissue has received little attention. We examined the association of early life exposure to TSP and TE with patterns of DNA methylation in breast tumors. METHODS: We conducted a study of women enrolled in the Western New York Exposures and Breast Cancer (WEB) Study. Methylation of nine genes (SFN, SCGB3A1, RARB, GSTP1, CDKN2A CCND2, BRCA1, FHIT, and SYK) was assessed using bisulfite-based pyrosequencing. TSP exposure at each woman's home address at birth, menarche, and when she had her first child was estimated. TE exposure was modeled for each woman's residence at menarche, her first birth, and twenty and ten years prior to diagnosis. Unconditional logistic regression was employed to estimate odds ratios (OR) of having methylation greater than the median value, adjusting for age, secondhand smoke exposure before age 20, current smoking status, and estrogen receptor status. RESULTS: Exposure to higher TSP at a woman's first birth was associated with lower methylation of SCGB3A1 (OR = 0.48, 95% CI: 0.23-0.99) and higher methylation of SYK (OR = 1.86, 95% CI: 1.03-3.35). TE at menarche was associated with increased methylation of SYK (OR = 2.37, 95% CI: 1.05-5.33). TE at first birth and ten years prior to diagnosis was associated with decreased methylation of CCND2 (OR ten years prior to diagnosis=0.48, 95% CI: 0.26-0.89). Although these associations were nominally significant, none were significant after adjustment for multiple comparisons (p < 0.01). CONCLUSIONS: We observed suggestive evidence that exposure to ambient air pollution throughout life, measured as TSP and TE, may be associated with DNA methylation of some tumor suppressor genes in breast tumor tissue. Future studies with a larger sample size that assess methylation of more sites are warranted.

Longitudinal assessment of occupational determinants of chlorpyrifos exposure in adolescent pesticide workers in Egypt.

Chlorpyrifos (CPF) is an organophosphourus insecticide applied to cotton fields by adolescents employed by the Egyptian Ministry of Agriculture. Urinary 3,5,6-trichloro-2-pyridinol (TCPy) is a biomarker of CPF exposure that has substantial variability among these applicators. In order to identify predictors of CPF exposure, we conducted a longitudinal study of 43 adolescent pesticide applicators in Egypt from April 2010 to January 2011 in Egypt. Urinary TCPy was quantified at 25 time-points, prior to, during, and following application. We used log-linear regression and a best subset selection approach to identify the exposure determinants that were most predictive of cumulative TCPy and participants' highest TCPy values (peak exposure). Applicators had cumulative urinary TCPy levels ranging from 167 to 49,8208µg/g creatinine. Total hours applying CPF (semi-partial r2=0.32), and total hours in the field applying other pesticides (semi-partial r2=0.08) were the strongest predictors of cumulative TCPy. Applicators had peak urinary TCPy levels ranging from 4 to 5715µg/g creatinine. The amount of time applying pesticides prior to blood draw was the strongest predictor of peak TCPy (semi-partial r2=0.30). We also observed evidence that wearing clean clothes to work was associated with lower longitudinal TCPy. Our results suggest there is an opportunity for targeted interventions, particularly related to hygiene or implementation of personal protective equipment usage to reduce CPF exposure among adolescent pesticide workers.

The impact of repeated organophosphorus pesticide exposure on biomarkers and neurobehavioral outcomes among adolescent pesticide applicators.

Egyptian adolescents are hired as seasonal workers to apply pesticides to the cotton crop and may perform this occupation for several years. However, few studies examined the effects of repeated pesticide exposure on health outcomes The goal of this study was to determine the impact of repeated pesticide exposure on neurobehavioral (NB) performance and biomarkers of exposure (urinary metabolite) and effect (cholinesterase activity). Eighty-four adolescents from two field stations in Menoufia, Egypt, were examined four times: before and during pesticide application season in 2010 and again before and during application season in 2011. At each of the four time points, participants completed a questionnaire, performed an NB test battery, and were assessed for urinary levels of the chlorpyrifos metabolite TCPy (3,5,6-trichloro-2-pyridinol) and blood cholinesterase activity. Following the study cohort over two consecutive pesticide application seasons revealed that TCPy levels significantly increased following exposure, and returned to baseline levels following the end of the application season. Blood butyryl cholinesterase activity exhibited a similar pattern. Although NB outcomes displayed learning and practice effects over time, deficits in performance were significantly associated with increased TCPy levels with reduction in the number of NB measures showing improvement over time. Biomarkers of exposure and effect demonstrated changes associated with pesticide application and recovery after application ended. Deficits in NB performance were correlated with elevated pesticide exposure. Data demonstrated that repeated pesticide exposure may exert a long-term adverse impact on human health.

Serum polychlorinated biphenyls and leukocyte telomere length in a highly-exposed population: The Anniston Community Health Survey.

BACKGROUND: Serum polychlorinated biphenyls (PCBs) have previously been associated with longer leukocyte telomere length (LTL) in most, but not all, of the few previous studies. PCBs were produced in Anniston, Alabama from 1929 to 1971 and participants of the Anniston Community Health Survey (ACHS) were highly exposed. OBJECTIVES: We evaluated serum levels of 35 PCBs and relative telomere length in 559 ACHS participants. METHODS: Relative LTL was measured in DNA extracted from blood clots. We assessed PCBs individually, grouped by chlorination, and summed PCBs. We used linear regression to assess the association between each PCB metric while adjusting for pertinent covariates. RESULTS: Serum PCBs were associated with longer LTL among white participants and the oldest age group of black participants. Among white participants, compared with those in the first quartile of sum PCBs those in the third quartile of sum PCBs had 8.09% longer relative LTL (95% CI: 1.99; 14.55) and those in the fourth had 7.58% longer relative LTL (95%CI: -0.01; 15.76) (p-quadratic=0.05). Among African American participants, serum PCBs were associated with longer relative LTL among those over age 64 only. Tests for interaction were not statistically significant. CONCLUSIONS: We observed a non-linear positive association between serum PCBs and LTL among white participants. Serum PCBs were associated with longer LTL in the oldest age group of African Americans. This association may provide insight into the cancers previously associated with exposure to PCBs, melanoma and non-Hodgkin lymphoma, which have been associated with long LTL in previous studies.