Background: Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban air pollutants from fossil fuel burning and other combustion sources. We previously reported that a broad spectrum of combustion-related DNA adducts in cord blood was associated with attention problems at 6–7 years of age in the Columbia Center for Children’s Environmental Health (CCCEH) longitudinal cohort study.
Objectives: We evaluated the relationship between behavioral problems and two different measures of prenatal exposure—both specific to PAH—in the same cohort.
Methods: Children of nonsmoking African-American and Dominican women in New York City (NYC) were followed from in utero to 6–7 years. Prenatal PAH exposure was estimated by personal air monitoring of the mothers during pregnancy as well as by the measurement of DNA adducts specific to benzo[a]pyrene (BaP), a representative PAH, in maternal and cord blood. At 6–7 years of age, child behavior was assessed using the Child Behavior Checklist (CBCL) (n = 253). Generalized linear models were used to test the association between prenatal PAH exposure and behavioral outcomes.
Results: In multivariate analyses, high prenatal PAH exposure, whether characterized by personal air monitoring (greater than the median of 2.27 ng/m3) or maternal and cord adducts (detectable or higher), was positively associated with symptoms of Anxious/Depressed and Attention Problems (p ≤ 0.05).
Conclusion: These results provide additional evidence that environmental levels of PAH encountered in NYC air can adversely affect child behavior.
air pollution; child behavior; PAH; prenatal
Exposure to polycyclic aromatic hydrocarbons (PAH) has been associated with allergic sensitization and asthma. We hypothesized that increased urinary PAH metabolites are associated with allergy or asthma among children age 5 yrs in an inner-city birth cohort. As part of an ongoing prospective birth cohort under the auspices of the Columbia Center for Children’s Environmental Health (CCCEH), urine was collected from 5-yr-old children (n = 222) of Dominican American and African American mothers in Northern Manhattan and South Bronx of New York City. Twenty-four PAH metabolites were measured in these specimens, and their levels (unadjusted and specific gravity corrected) were evaluated with IgE levels and asthma outcomes. Ten metabolites were detected in urine from all children. Concentrations ranged higher than those in representative samples of US children ages 6–11 in the National Health and Nutrition Examination Survey (NHANES). Among CCCEH children, compared with African Americans, the Dominican children had higher 2-hydroxynaphthalene but lower 9-hydroxyfluorene and 4-hydroxyphenanthrene concentrations. Increased 3-hydroxyfluorene and 3-hydroxyphenanthrene levels were associated with higher anti-mouse IgE levels (p < 0.05). These plus 2-hydroxynaphthalene, 2-hydroxyflourene and 1-hydroxyphenanthrene concentrations were associated with higher anti-mouse IgE levels on multivariate analyzes. Increased 2-hydroxyphenanthrene, 3-hydroxyphenanthrene and 4-hydroxyphenanthrene levels were associated with higher anti-cat IgE levels (p < 0.05) in univariate, but not multivariate, analyzes. Levels of PAH metabolites were not associated with respiratory symptoms. Measures of PAH metabolites suggest considerable exposure in an urban pediatric population, and possible associations with allergic sensitization to mouse.
polycyclic aromatic hydrocarbons; inner-city asthma; allergen-specific IgE
Exposure to traffic-related air pollutants, including polycyclic aromatic hydrocarbons (PAHs), can induce asthma. However, the effects of early repeated PAH exposure over time on different asthma phenotypes have not been examined.
To assess associations between repeated PAH exposure, measured from prenatal personal and residential indoor monitors in children's homes, and asthma in an inner-city cohort.
Prenatal exposure was assessed by personal air monitoring during 48 hours and exposure at 5 to 6 years of age by 2-week residential monitoring in the Columbia Center for Children's Environmental Health cohort. PAH was dichotomized into pyrene (representative semivolatile PAH) and the sum of 8 nonvolatile PAHs. High exposure to each was defined as measures above the median at both repeated time points. Asthma and wheeze were determined by validated questionnaires at ages 5 to 6 years. Children with specific IgE levels greater than 0.35 IU/mL to any of 5 indoor allergens were considered seroatopic.
Among all 354 children, repeated high exposure to pyrene was associated with asthma (odds ratio [OR], 1.90; 95% confidence interval [CI], 1.13-3.20). Among 242 nonatopic children, but not those sensitized to indoor allergens (n = 87) or with elevated total IgE levels (n = 171), high pyrene levels were associated positively with asthma (OR, 2.89; 95% CI, 1.77-5.69), asthma medication use (OR, 2.28; 95% CI, 1.13-4.59), and emergency department visits for asthma (OR, 2.43; 95% CI, 1.20-4.91). Associations between the levels of the 8 nonvolatile PAHs and asthma were not observed, even when stratifying by seroatopy.
Nonatopic children may be more susceptible to the respiratory consequences of early pyrene exposures.
Polycyclic aromatic hydrocarbons (PAH) originate from the incomplete combustion of organic matter and ambient air pollution by these is increasing. There is also an increase in the global prevalence of asthma, for which environmental pollution has been recognized as one of the important factors. Exposure to pollutants and other allergens induces chronic airway inflammation by generation of reactive oxygen species, causing oxidative stress. Therefore, the objective of the present study was to assess association, if any, between exposure to PAH and asthma as well as oxidative stress in children.
In this hospital-based case control study, cases of bronchial asthma aged 1–14 years and healthy matched controls were included. Oxidative stress was measured by assessing the levels of enzymes catalase, superoxide dismutase, malondialdehyde (MDA), and reduced glutathione (GSH).
Forty-two cases and 20 controls were enrolled. Mean blood level of phenanthrene, a PAH, was 63.11 ppb ± 115.62 and 4.20 ppb ± 10.68 ppb in cases and controls, respectively (P = 0.02). Mean blood levels of GSH was significantly lower in cases and controls (27.39 μg/ml ± 11.09 versus 47.39 g/ml ± 13.83; P-value = 0.001). Likewise, mean blood level of MDA in nanomole/ml was significantly higher in asthma as compared with controls (12.85 ± 5.40 versus 8.19 ± 5.16; P-value = 0.002), suggestive of increased oxidative stress.
Because elevated blood level of phenanthrene is associated with bronchial asthma as well as with oxidative stress, measures to reduce exposure to PAH may possibly lead to reduced incidence and severity of bronchial asthma.
Asthma; children; India; phenanthrene; polycyclic aromatic hydrocarbons; oxidative stress
Early life exposure to ambient polycyclic aromatic hydrocarbons (PAHs) can result in developmental delay. The negative health effects of PAHs have been well-documented but the cost of developmental delay due to PAH exposure has not been studied. The Columbia Center for Children’s Environmental Health previously has reported the significant effect of prenatal exposure to ambient PAHs on delayed mental development at three years, using the Bayley Scales in a cohort of low-income women and children in New York City (NYC). Here we have used the cohort results to estimate the annual costs of preschool special education services for low-income NYC children with developmental delay due to PAH exposure using the Environmentally Attributable Fraction method. The estimated cost of PAH-exposure-related services is over $13.7 million per year for Medicaid births in NYC. This high cost supports policies to reduce level of PAHs in NYC air.
PAH; developmental delay; costs
Previously, we reported that prenatal exposures to polycyclic aromatic hydrocarbons (PAH) and postnatal environmental tobacco smoke (ETS) in combination were associated with respiratory symptoms at ages 1 and 2 years. Here, we hypothesized that children exposed to both prenatal PAH and ETS may be at greater risk of asthma and seroatopy at ages 5 to 6 years, after controlling for current pollution exposure.
Prenatal PAH exposure was measured by personal air monitoring over 48 hrs. ETS exposure, respiratory symptoms and asthma at ages 5–6 years were assessed through questionnaire. Immunoglobulin (Ig) E was measured by Immunocap.
A significant interaction between prenatal PAH and prenatal (but not postnatal) ETS exposure on asthma (p<0.05), but not IgE, was detected. Among children exposed to prenatal ETS, a positive nonsignificant association was found between prenatal PAH exposure and asthma (OR 1.96, 95% CI [0.95–4.05]). Among children without exposure to prenatal ETS, a negative nonsignificant association was found between prenatal PAH exposure and asthma (OR 0.65, 95% CI [0.41–1.01]). Prenatal PAH exposure was not associated with asthma or IgE at age 5 to 6 years.
Combined prenatal exposure to PAH and ETS appears to be associated with asthma but not seroatopy at age 5–6. Exposure to PAH alone does not appear associated with either asthma or seroatopy at age 5 to 6 years. Discerning the differential effects between ETS exposed and ETS nonexposed children requires further study.
Several studies have found associations between diesel exposure, respiratory symptoms, and/or impaired pulmonary function. We hypothesized that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAH), important components of diesel exhaust and other combustion sources, may be associated with respiratory symptoms in young children. We also hypothesized that exposure to environmental tobacco smoke (ETS) may worsen symptoms beyond that observed to be associated with PAH alone.
To test our hypotheses, we recruited 303 pregnant women from northern Manhattan believed to be at high risk for exposure to both PAH and ETS, collected 48-h personal PAH exposure measurements, and monitored their children prospectively.
By 12 months of age, more cough and wheeze were reported in children exposed to prenatal PAH in concert with ETS postnatally (PAH × ETS interaction odds ratios [ORs], 1.41 [p < 0.01] and 1.29 [p < 0.05], respectively). By 24 months, difficulty breathing and probable asthma were reported more frequently among children exposed to prenatal PAH and ETS postnatally (PAH × ETS ORs, 1.54 and 1.64, respectively [p < 0.05]).
Our results suggest that early exposure to airborne PAH and ETS can lead to increased respiratory symptoms and probable asthma by age 12 to 24 months. Interventions to lower the risk of respiratory disease in young children living in the inner city may need to address the importance of multiple environmental exposures.
asthma; environmental tobacco smoke; polycyclic aromatic hydrocarbons
Background: Airborne polycyclic aromatic hydrocarbons (PAH) are widespread urban pollutants that can bind to DNA to form PAH–DNA adducts. Prenatal PAH exposure measured by personal monitoring has been linked to cognitive deficits in childhood in a prospective study conducted by the Columbia Center for Children’s Environmental Health.
Objectives: We measured PAH–DNA and other bulky aromatic adducts in umbilical cord white blood cells using the 32P-postlabeling assay to determine the association between this molecular dosimeter and behavioral/attention problems in childhood.
Methods: Children born to nonsmoking African-American and Dominican women residing in New York City (NYC) were followed from in utero to 7–8 years of age. At two time points before 8 years of age (mean ages, 4.8 years and 7 years), child behavior was assessed using the Child Behavior Checklist (CBCL). To estimate and test the association between adducts and behavioral outcomes, both CBCL continuous raw scores and dichotomized T-scores were analyzed.
Results: Higher cord adducts were associated with higher symptom scores of Anxious/Depressed at 4.8 years and Attention Problems at 4.8 and 7 years, and with Diagnostic and Statistical Manual of Mental Disorders, 4th edition–oriented Anxiety Problems at 4.8 years.
Conclusions: These results suggest that PAH exposure, measured by DNA adducts, may adversely affect child behavior, potentially affecting school performance.
cord blood; DNA adducts; neurodevelopment; PAH; 32P-postlabeling
Environmental pollutants such as polycyclic aromatic hydrocarbons (PAHs), lead, and mercury are released by combustion of coal and other fossil fuels.
In the present study we evaluated the association between prenatal exposure to these pollutants and child development measured by the Gesell Developmental Schedules at 2 years of age.
The study was conducted in Tongliang, Chongqing, China, where a seasonally operated coal-fired power plant was the major source of ambient PAHs and also contributed lead and mercury to the air. In a cohort of nonsmoking women and their newborns enrolled between March 2002 and June 2002, we measured levels of PAH–DNA adducts, lead, and mercury in umbilical cord blood. PAH–DNA adducts (specifically benzo[a]pyrene adducts) provided a biologically relevant measure of PAH exposure. We also obtained developmental quotients (DQs) in motor, adaptive, language, and social areas.
Decrements in one or more DQs were significantly associated with cord blood levels of PAH–DNA adducts and lead, but not mercury. Increased adduct levels were associated with decreased motor area DQ (p = 0.043), language area DQ (p = 0.059), and average DQ (p = 0.047) after adjusting for cord lead level, environmental tobacco smoke, sex, gestational age, and maternal education. In the same model, high cord blood lead level was significantly associated with decreased social area DQ (p = 0.009) and average DQ (p = 0.038).
The findings indicate that exposure to pollutants from the power plant adversely affected the development of children living in Tongliang; these findings have implications for environmental health policy.
China; coal burning; lead; mercury; neurodevelopment; PAH–DNA adducts; prenatal
Background: Polycyclic aromatic hydrocarbons (PAHs) are carcinogenic environmental pollutants generated during incomplete combustion. After exposure and during metabolism, PAHs can form reactive epoxides that can covalently bind to DNA. These PAH–DNA adducts are established markers of cancer risk. PAH exposure has been associated with epigenetic alterations, including genomic cytosine methylation. Both global hypomethylation and hypermethylation of specific genes have been associated with cancer and other diseases in humans. Experimental evidence suggests that PAH–DNA adduct formation may preferentially target methylated genomic regions. Early embryonic development may be a particularly susceptible period for PAH exposure, resulting in both increased PAH–DNA adducts and altered DNA methylation.
Objective: We explored whether prenatal exposure to PAHs is associated with genomic DNA methylation in cord blood and whether methylation levels are associated with the presence of detectable PAH–DNA adducts.
Methods: In a longitudinal cohort study of nonsmoking women in New York City, we measured PAH exposure during pregnancy using personal air monitors, assessed PAH internal dose using prenatal urinary metabolites (in a subset), and quantified benzo[a]pyrene–DNA adducts and genomic DNA methylation in cord blood DNA among 164 participants.
Results: Prenatal PAH exposure was associated with lower global methylation in umbilical cord white blood cells (p = 0.05), but global methylation levels were positively associated with the presence of detectable adducts in cord blood (p = 0.01).
Conclusions: These observations suggest that PAH exposure was adequate to alter global methylation in our study population. Additional epidemiologic studies that can measure site-specific cytosine methylation and adduct formation will improve our ability to understand this complex molecular pathway in vivo.
adducts; epigenetics; methylation; polycyclic aromatic hydrocarbons; prenatal; umbilical cord blood
Rates of developmental and respiratory diseases are disproportionately high in underserved, minority populations such as those in New York City's Washington Heights, Harlem, and the South Bronx. Blacks and Latinos in these neighborhoods represent high risk groups for asthma, adverse birth outcomes, impaired development, and some types of cancer. The Columbia Center for Children's Environmental Health in Washington Heights uses molecular epidemiologic methods to study the health effects of urban indoor and outdoor air pollutants on children, prenatally and postnatally, in a cohort of over 500 African-American and Dominican (originally from the Dominican Republic) mothers and newborns. Extensive data are collected to determine exposures to particulate matter < 2.5 microm in aerodynamic diameter (PM(2.5)), polycyclic aromatic hydrocarbons (PAHs), diesel exhaust particulate (DEP), nitrogen oxide, nonpersistent pesticides, home allergens (dust mite, mouse, cockroach), environmental tobacco smoke (ETS), and lead and other metals. Biomarkers, air sampling, and clinical assessments are used to study the effects of these exposures on children's increased risk for allergic sensitization, asthma and other respiratory disorders, impairment of neurocognitive and behavioral development, and potential cancer risk. The center conducts its research and community education in collaboration with 10 community-based health and environmental advocacy organizations. This unique academic-community partnership helps to guide the center's research so that it is most relevant to the context of the low-income, minority neighborhoods in which the cohort resides, and information is delivered back to these communities in meaningful ways. In turn, communities become better equipped to relay environmental health concerns to policy makers. In this paper we describe the center's research and its academic-community partnership and present some preliminary findings.
Chromosomal aberrations are associated with increased cancer risk in adults. Previously, we demonstrated that stable aberrations involving chromosomes 1-6 in cord blood are associated with prenatal exposure to polycyclic aromatic hydrocarbons (PAHs) measured in air and are disproportionate to genomic content. We now examine whether the association with air PAHs is chromosome-specific and extends to smaller chromosomes.
Using Whole Chromosome Paints for chromosomes 1-6, 11,12,14,19, and a 6q sub-telomere specific probe, we scored 48 cord bloods (1500 metaphases per sample) from newborns monitored prenatally for airborne PAH exposure in the Columbia Center for Children’s Environmental Health cohort. Frequencies of stable aberrations were calculated as incident aberrations per 100 Cell Equivalents scored, and examined for association with airborne PAHs.
Aberrations in chromosome 6 occurred more frequently than predicted by genomic content (p<0.008). Levels of both prenatal airborne PAHs and stable aberration frequency in chromosomes 1-6 decreased to half the levels reported previously in the same cohort (mean PAH decreased from 3.6 to 1.8 ng/m3; mean stable aberration frequency from 0.56 to 0.24, SD=0.19). The mean stable aberration frequency was 0.45 (SD=0.15) in chromosomes 11-19. After adjusting for gender, ethnicity, and household smokers, the mean stable aberration frequency increased with increasing PAH exposure: with a doubling of prenatal PAH exposure, the mean stable aberration frequency for the chromosome1-6 group increased by a factor of 1.49 (95%CI: 0.84, 2.66; p=0.17); for chromosomes 11-19 mean stable aberration frequency increased by 2.00 (95%CI:1.11, 3.62; p=0.02); for chromosome 6 alone, it increased by 3.16 (95%CI: 0.93,10.77; p= 0.06); there was no increase for chromosomes1-5 (p>0.8). Aberrations in chromosomes 11,12,14,19 and 6 were associated with prenatal exposure to PAHs in air, even at lower levels of PAH in air. The observed chromosome-specific effects of prenatal airborne PAHs raise concern about potential cancer risk.
Chromosomal aberrations; Polycyclic aromatic hydrocarbons; Cohort study; Prenatal
In a longitudinal cohort of ∼700 children in New York City, the prevalence of asthma (>25%) is among the highest in the US. This high risk may in part be caused by transplacental exposure to traffic-related polycyclic aromatic hydrocarbons (PAHs) but biomarkers informative of PAH-asthma relationships is lacking. We here hypothesized that epigenetic marks associated with transplacental PAH exposure and/or childhood asthma risk could be identified in fetal tissues. Mothers completed personal prenatal air monitoring for PAH exposure determination. Methylation sensitive restriction fingerprinting was used to analyze umbilical cord white blood cell (UCWBC) DNA of 20 cohort children. Over 30 DNA sequences were identified whose methylation status was dependent on the level of maternal PAH exposure. Six sequences were found to be homologous to known genes having one or more 5′-CpG island(s) (5′-CGI). Of these, acyl-CoA synthetase long-chain family member 3 (ACSL3) exhibited the highest concordance between the extent of methylation of its 5′-CGI in UCWBCs and the level of gene expression in matched fetal placental tissues in the initial 20 cohort children. ACSL3 was therefore chosen for further investigation in a larger sample of 56 cohort children. Methylation of the ACSL3 5′-CGI was found to be significantly associated with maternal airborne PAH exposure exceeding 2.41 ng/m3 (OR = 13.8; p<0.001; sensitivity = 75%; specificity = 82%) and with a parental report of asthma symptoms in children prior to age 5 (OR = 3.9; p<0.05). Thus, if validated, methylated ACSL3 5′CGI in UCWBC DNA may be a surrogate endpoint for transplacental PAH exposure and/or a potential biomarker for environmentally-related asthma. This exploratory report provides a new blueprint for the discovery of epigenetic biomarkers relevant to other exposure assessments and/or investigations of exposure-disease relationships in birth cohorts. The results support the emerging theory of early origins of later life disease development.
Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous air pollutants generated by combustion of organic material, including fossil fuel.
It has been an open question whether prenatal exposure to air pollution in general and PAHs in particular significantly increases the risk of intrauterine growth restriction, including small size for gestational age (SGA), and preterm delivery. Here, we have examined this hypothesis in a cohort of mothers and newborns in New York City.
Subjects were young, nonsmoking, healthy African-American (n = 224) and Dominican (n = 392) mother–newborn pairs residing in New York City whose prenatal PAH exposures were estimated by personal air monitoring. Questionnaire and medical record data were obtained.
A 1 natural-log (ln)-unit increase in prenatal PAH exposure was associated with a 2-fold increase in risk of symmetric intrauterine growth restriction (i.e., SGA and fetal growth ratio < 85%) among full-term African Americans (p < 0.05). Preterm delivery risk was 5-fold greater among African Americans per ln-unit increase in prenatal PAH exposure. The same unit increase in exposure significantly increased the ratio of head circumference to birth weight by 0.04% in African Americans. These effects were not observed in Dominicans.
Prenatal PAH exposure is likely to contribute to the occurrence of SGA as well as preterm births among African Americans. The lack of an association in Dominicans might reflect modification of the risk by healthful cultural practices among recent Dominican immigrants. Given that PAHs are globally generated and distributed pollutants, our observations have potential implications for environmental health and energy policies.
air pollution; cephalization index; fetal growth ratio; large for gestational age; polycyclic aromatic hydrocarbons; ponderal index; preterm birth; small for gestational age; symmetric intra-uterine growth restriction
Traffic-related air pollutants have been associated with adverse health effects. We hypothesized that exposure to polycyclic aromatic hydrocarbons (PAHs), elemental carbon (EC, diesel indicator), particulate matter (PM2.5), and a suite of metals declined from 1998 to 2006 in NYC due to policy interventions. PAH levels from personal monitoring of pregnant mothers participating in the Columbia’s Center for Children’s Environmental Health birth cohort study, and EC, PM2.5, and metal data from five New York State Department of Environmental Conservation stationary monitors were compared across sites and over time (1998–2006). Univariate analysis showed a decrease in personal PAHs exposures from 1998 to 2006 (p < 0.0001). After controlling for environmental tobacco smoke, indoor heat, and cooking, year of personal monitoring remained a predictor of decline in Σ8PAHs (β = −0.269, p < 0.001). Linear trend analysis also suggested that PM2.5 declined (p = 0.09). Concentrations of EC and most metals measured by stationary site monitors, as measured by ANOVA, did not decline. Across stationary sites, levels of airborne EC and metals varied considerably. By contrast PM2.5 levels were highly intercorrelated (values ranged from 0.725 to 0.922, p < 0.01). Further policy initiatives targeting traffic-related air pollutants may be needed for a greater impact on public health.
Coal burning provides 70% of the energy for China’s industry and power, but releases large quantities of polycyclic aromatic hydrocarbons (PAHs) and other pollutants. PAHs are reproductive and developmental toxicants, mutagens, and carcinogens.
We evaluated the benefit to neurobehavioral development from the closure of a coal-fired power plant that was the major local source of ambient PAHs.
The research was conducted in Tongliang, Chongqing, China, where a coal-fired power plant operated seasonally before it was shut down in May 2004. Two identical prospective cohort studies enrolled nonsmoking women and their newborns in 2002 (before shutdown) and 2005 (after shutdown). Prenatal PAH exposure was measured by PAH–DNA adducts (benzo[a]pyrene–DNA) in umbilical cord blood. Child development was assessed by the Gesell Developmental Schedules at 2 years of age. Prenatal exposure to other neurotoxicants and potential confounders (including lead, mercury, and environmental tobacco smoke) was measured. We compared the cohorts regarding the association between PAH–DNA adduct levels and neurodevelopmental outcomes.
Significant associations previously seen in 2002 between elevated adducts and decreased motor area developmental quotient (DQ) (p = 0.043) and average DQ (p = 0.047) were not observed in the 2005 cohort (p = 0.546 and p = 0.146). However, the direction of the relationship did not change.
The findings indicate that neurobehavioral development in Tongliang children benefited by elimination of PAH exposure from the coal-burning plant, consistent with the significant reduction in PAH–DNA adducts in cord blood of children in the 2005 cohort. The results have implications for children’s environmental health in China and elsewhere.
China; coal burning; lead; neurobehavioral development; PAH-DNA adducts; prenatal
Polycyclic aromatic hydrocarbons (PAHs) are combustion products of organic materials, mixtures of which contain multiple known and probable human carcinogens. PAHs occur in indoor and outdoor air, as well as in char-broiled meats and fish. Human exposure to PAHs occurs by inhalation, ingestion and topical absorption, and subsequently formed metabolites are either rendered hydrophilic and excreted, or bioactivated and bound to cellular macromolecules. The formation of PAH-DNA adducts (DNA binding products), considered a necessary step in PAH-initiated carcinogenesis, has been widely studied in experimental models and has been documented in human tissues. This review describes immunohistochemistry (IHC) studies, which reveal localization of PAH-DNA adducts in human tissues, and semi-quantify PAH-DNA adduct levels using the Automated Cellular Imaging System (ACIS). These studies have shown that PAH-DNA adducts concentrate in: basal and supra-basal epithelium of the esophagus, cervix and vulva; glandular epithelium of the prostate; and cytotrophoblast cells and syncitiotrophoblast knots of the placenta. The IHC photomicrographs reveal the ubiquitous nature of PAH-DNA adduct formation in human tissues as well as PAH-DNA adduct accumulation in specific, vulnerable, cell types. This semi-quantative method for PAH-DNA adduct measurement could potentially see widespread use in molecular epidemiology studies.
DNA damage; human tissues; immunohistochemistry; immunoassay; PAH-DNA adducts; semi-quantitation; molecular epidemiology
Residential wood combustion is one of the important sources of air pollution in developing countries. Among the pollutants emitted, parent polycyclic aromatic hydrocarbons (pPAHs) and their derivatives, including nitrated and oxygenated PAHs (nPAHs and oPAHs), are of concern because of their mutagenic and carcinogenic effects. In order to evaluate their impacts on regional air quality and human health, emission inventories, based on realistic emission factors (EFs), are needed. In this study, the EFs of 28 pPAHs (EFPAH28), 9 nPAHs (EFPAHn9) and 4 oPAHs (EFPAHo4) were measured for residential combustion of 27 wood fuels in rural China. The measured EFPAH28, EFPAHn9, and EFPAHo4 for brushwood were 86.7±67.6, 3.22±1.95×10−2, and 5.56±4.32 mg/kg, which were significantly higher than 12.7±7.0, 8.27±5.51×10−3, and 1.19±1.87 mg/kg for fuel wood combustion (p < 0.05). Sixteen U.S. EPA priority pPAHs contributed approximately 95% of the total of the 28 pPAHs measured. EFs of pPAHs, nPAHs, and oPAHs were positively correlated with one another. Measured EFs varied obviously depending on fuel properties and combustion conditions. The EFs of pPAHs, nPAHs, and oPAHs were significantly correlated with modified combustion efficiency and fuel moisture. Nitro-naphthalene and 9-fluorenone were the most abundant nPAHs and oPAHs identified. Both nPAHs and oPAHs showed relatively high tendencies to be present in the particulate phase than pPAHs due to their lower vapor pressures. The gas-particle partitioning of freshly emitted pPAHs, nPAHs and oPAHs was primarily controlled by organic carbon absorption.
Our prospective cohort study of nonsmoking African-American and Dominican
mothers and children in New York City is evaluating the role of prenatal
exposure to urban pollutants, including polycyclic aromatic hydrocarbons (PAHs), environmental tobacco smoke (ETS), and pesticides, in
the pathogenesis of neurobehavioral disorders. We used the Bayley Scales
of Infant Development to evaluate the effects on child mental and
psychomotor development of prenatal exposure to airborne PAHs monitored
during pregnancy by personal air sampling. Behavioral development was
assessed by the Child Behavior Checklist. We adjusted for potential
confounders including sociodemographic factors and prenatal exposure to
ETS and chlorpyrifos. Prenatal exposure to PAHs was not associated with
psychomotor development index or behavioral problems. However, high
prenatal exposure to PAHs (upper quartile) was associated with lower
mental development index at age 3 [β= –5.69; 95% confidence interval (CI), –9.05 to –2.33; p < 0.01]. The odds of cognitive developmental delay were also
significantly greater for children with high prenatal exposure (odds
ratio = 2.89; 95% CI, 1.33 to 6.25; p = 0.01). General estimated equation analysis showed a significant
age × PAH effect on mental development (p = 0.01), confirming the age-specific regression findings. Further
adjustment for lead did not alter the relationships. There were no
differences in effect sizes by ethnicity. The results require confirmation
but suggest that environmental PAHs at levels recently encountered
in New York City air may adversely affect children’s cognitive
development at 3 years of age, with implications for school performance.
air pollution; neurodevelopment; polycyclic aromatic hydrocarbons; prenatal
Polycyclic aromatic hydrocarbons (PAHs) are formed during incomplete combustion. Domestic wood burning and road traffic are the major sources of PAHs in Sweden. In Stockholm, the sum of 14 different PAHs is 100-200 ng/m(3) at the street-level site, the most abundant being phenanthrene. Benzo[a]pyrene (B[a]P) varies between 1 and 2 ng/m(3). Exposure to PAH-containing substances increases the risk of cancer in humans. The carcinogenicity of PAHs is associated with the complexity of the molecule, i.e., increasing number of benzenoid rings, and with metabolic activation to reactive diol epoxide intermediates and their subsequent covalent binding to critical targets in DNA. B[a]P is the main indicator of carcinogenic PAHs. Fluoranthene is an important volatile PAH because it occurs at high concentrations in ambient air and because it is an experimental carcinogen in certain test systems. Thus, fluoranthene is suggested as a complementary indicator to B[a]P. The most carcinogenic PAH identified, dibenzo[a,l]pyrene, is also suggested as an indicator, although it occurs at very low concentrations. Quantitative cancer risk estimates of PAHs as air pollutants are very uncertain because of the lack of useful, good-quality data. According to the World Health Organization Air Quality Guidelines for Europe, the unit risk is 9 X 10(-5) per ng/m(3) of B[a]P as indicator of the total PAH content, namely, lifetime exposure to 0.1 ng/m(3) would theoretically lead to one extra cancer case in 100,000 exposed individuals. This concentration of 0.1 ng/m(3) of B[a]P is suggested as a health-based guideline. Because the carcinogenic potency of fluoranthene has been estimated to be approximately 20 times less than that of B[a]P, a tentative guideline value of 2 ng/m(3) is suggested for fluoranthene. Other significant PAHs are phenanthrene, methylated phenanthrenes/anthracenes and pyrene (high air concentrations), and large-molecule PAHs such as dibenz[a,h]anthracene, benzo[b]fluoranthene, benzo[k]fluoranthene, and indeno[1,2,3-cd]pyrene (high carcinogenicity). Additional source-specific indicators are benzo[ghi]perylene for gasoline vehicles, retene for wood combustion, and dibenzothiophene and benzonaphthothiophene for sulfur-containing fuels.
Polycyclic aromatic hydrocarbons (PAHs) are pollutants created by the incomplete combustion of carbon, and are increasing in the environment largely due to the burning of fossil fuels. PAHs occur as complex mixtures, and some combinations have been shown to cause synergistic developmental toxicity in fish embryos, characterized by pericardial edema and craniofacial malformations. Previous studies have indicated that in the zebrafish model, this toxicity is mediated by the aryl hydrocarbon receptor 2 (AHR2), and enhanced by inhibition of CYP1A activity. In this study, we further examined this interaction of the model PAH and AHR agonist β-naphthoflavone (BNF) with and without the AHR partial agonist/antagonist and CYP1A inhibitor α-naphthoflavone (ANF) to determine 1) whether ANF was acting as an AHR antagonist, 2) what alterations BNF and ANF both alone and in combination had on mRNA expression of the AHR regulated genes cytochrome P450 (cyp) 1a, 1b1, and 1c1, and the AHR repressor (ahrr2) prior to vs. during deformity onset, and 3) compare CYP1A enzyme activity with mRNA induction. Zebrafish embryos were exposed from 24–48 or 24–96 hpf to BNF, 1–100 μg/L, ANF, 1–150 μg/L, a BNF+ANF co-exposure (1 μg/L + 100 μg/L), or a DMSO solvent control. RNA was extracted and examined by quantitative real time PCR. Both BNF and ANF each individually resulted in a dose dependent increase CYP1A, CYP1B1, CYP1C1, and AHRR2 mRNA, confirming their activities as AHR agonists. In the BNF+ANF co-exposures prior to deformity onset, expression of these genes was synergistic, and expression levels of the AHR regulated genes resembled the higher doses of BNF alone. Gene induction during deformities was also significantly increased in the co-exposure, but to a lesser magnitude than prior to deformity onset. EROD measurements of CYP1A activity showed ANF inhibited activity induction by BNF in the co-exposure group; this finding is not predicted by mRNA expression, which is synergistically induced in this treatment. This suggests that inhibition of CYP1A activity may alter metabolism and/or increase the half-life of the AHR agonist(s), allowing for increased AHR activation. This study furthers a mechanistic understanding of interactions underlying PAH synergistic toxicity.
quantitative real-time PCR; CYP1A; CYP1B1; CYP1C1; AHRR; zebrafish; polycyclic aromatic hydrocarbons; aryl hydrocarbon receptor
Occupational and environmental exposure to polycyclic aromatic hydrocarbons (PAHs) has been suggested to provoke inflammatory and/or allergic disorders, including asthma, rhinitis, and dermatitis. The molecular mechanisms of this PAH-mediated inflammation remain to be clarified. Previous studies implied the involvement of PAHs as irritants and allergens, with the reactive oxygen species generated from the oxygenated PAHs believed to be an exacerbating factor. It is also possible that PAHs contribute to the pathogenesis through activation of aryl-hydrocarbon receptor (AhR)-mediated transcription, since PAHs are potent inducers of the AhR. To address this point, we generated transgenic mouse lines expressing the constitutive active form of the AhR in keratinocytes. In these lines of mice, the AhR activity was constitutively enhanced in the absence of ligands, so that any other direct effects of PAHs and their metabolites could be ignored. At birth, these transgenic mice were normal, but severe skin lesions with itching developed postnatally. The skin lesions were accompanied by inflammation and immunological imbalance and resembled typical atopic dermatitis. We demonstrate that constitutive activation of the AhR pathway causes inflammatory skin lesions and suggests a new mechanism for the exacerbation of inflammatory diseases after exposure to occupational and environmental xenobiotics.
Polycyclic aromatic hydrocarbons (PAHs) are an important class of toxic
pollutants released by fossil fuel combustion. Other pollutants include
metals and particulate matter. PAH–DNA adducts, or benzo[a]pyrene (BaP) adducts as their proxy, provide a chemical-specific
measure of individual biologically effective doses that have been associated
with increased risk of cancer and adverse birth outcomes. In
the present study we examined the relationship between prenatal PAH exposure
and fetal and child growth and development in Tongliang, China, where
a seasonally operated coal-fired power plant was the major pollution
source. In a cohort of 150 nonsmoking women and their newborns
enrolled between 4 March 2002 and 19 June 2002, BaP–DNA adducts
were measured in maternal and umbilical cord blood obtained at delivery. The
number of gestational months occurring during the period of power
plant operation provided a second, more general measure of exposure
to plant emissions, in terms of duration. High PAH–DNA adduct
levels (above the median of detectable adduct level) were associated
with decreased birth head circumference (p = 0.057) and reduced children’s weight at 18 months, 24 months, and 30 months
of age (p < 0.05), after controlling for potential confounders. In addition, in
separate models, longer duration of prenatal exposure was associated
with reduced birth length (p = 0.033) and reduced children’s height at 18 (p = 0.001), 24 (p < 0.001), and 30 months of age (p < 0.001). The findings suggest that exposure to elevated levels of
PAHs, with the Tongliang power plant being a significant source, is associated
with reduced fetal and child growth in this population.
birth outcome; coal-burning emission; cord blood; fetal and child development; PAH-DNA adducts
Chromosome aberrations are associated with environmental exposures in infants and children. Recently we reported that prenatal exposure to airborne polycyclic aromatic hydrocarbons (PAHs) was significantly (P < 0.01) associated with stable aberration frequencies in cord blood from a subset of 60 newborns from the Columbia Center for Children's Environmental Health Prospective Cohort Study (Bocskay K et al. : Cancer Epidemiol Biomarkers Prev 14:506–511). To determine whether the environmental exposures may be targeting specific chromosomes and to compare various methods for measuring chromosome aberrations, we further evaluated this same subset of subjects composed of African-American and Dominican nonsmoking mother–newborn pairs residing in low-income neighborhoods of New York City, and exposed to varying levels of airborne PAHs. Chromosome aberrations were measured in cord blood lymphocytes, both by whole chromosome probe (WCP) fluorescence in situ hybridization (FISH) and traditional Giemsa-staining. Prenatal exposures were assessed by personal air monitoring. Breaks in chromosomes 1–6, as detected by WCP FISH, were nonrandomly distributed, underscoring the importance of appropriate chromosome probe selection to capture cytogenetic damage in response to exposure. FISH for stable aberrations was found to be a more sensitive method for detecting aberration frequencies associated with environmental exposures, when compared with FISH for unstable aberrations or Giemsa-staining for aberrations. Together, these results suggest that PAHs may be targeting specific chromosomes and highlight the importance of using the more sensitive detection methods to assess risk in populations with low levels of exposure.
chromosome aberrations; fluorescence in situ hybridization; Giemsa-staining
Current understanding on health effects of long-term polycyclic aromatic hydrocarbon (PAH) exposure is limited by lack of data on time-varying nature of the pollutants at an individual level. In a cohort of pregnant women in Krakow, Poland, we examined the contribution of temporal, spatial, and behavioral factors to prenatal exposure to airborne PAHs within each trimester and developed a predictive model of PAH exposure over the entire gestational period.
We monitored nonsmoking pregnant women (n = 341) for their personal exposure to pyrene and eight carcinogenic PAHs—benz[a]anthracene, chrysene/isochrysene, benzo[b]fluoranthene, benzo[k]fluoranthene, benzo[a]pyrene [B(a)P], indeno[1,2,3-c,d]pyrene, dibenz[a,h]anthracene, and benzo[g,h,i]perylene—during their second trimester for a consecutive 48-hr period. In a subset (n = 78), we monitored indoor and outdoor levels simultaneously with the personal monitoring during the second trimester with an identical monitor. The subset of women was also monitored for personal exposure for a 48-hr period during each trimester. We repeatedly administered a questionnaire on health history, lifestyle, and home environment.
The observed personal, indoor, and outdoor B(a)P levels we observed in Krakow far exceed the recommended Swedish guideline value for B(a)P of 0.1 ng/m3. Based on simultaneously monitored levels, the outdoor PAH level alone accounts for 93% of total variability in personal exposure during the heating season. Living near the Krakow bus depot, a crossroad, and the city center and time spent outdoors or commuting were not associated with higher personal exposure. During the nonheating season only, a 1-hr increase in environmental tobacco smoke (ETS) exposure was associated with a 10–16% increase in personal exposure to the nine measured PAHs. A 1°C decrease in ambient temperature was associated with a 3–5% increase in exposure to benz[a]anthracene, benzo[k]fluoranthene, and dibenz[a,h]anthracene, after accounting for the outdoor concentration. A random effects model demonstrated that mean personal exposure at a given gestational period depends on the season, residence location, and ETS.
Considering that most women reported spending < 3 hr/day outdoors, most women in the study were exposed to outdoor-originating PAHs within the indoor setting. Cross-sectional, longitudinal monitoring supplemented with questionnaire data allowed development of a gestation-length model of individual-level exposure with high precision and validity. These results are generalizable to other nonsmoking pregnant women in similar exposure settings and support reduction of exposure to protect the developing fetus.
coal; long-term personal exposure; polycyclic aromatic hydrocarbons; spatial and temporal variability