Aromatase (CYP19) is a key enzyme in estrogens biosynthesis. In the mammary gland,
gene is expressed at low levels under the regulation of its I.4 promoter. In hormone-dependent breast cancer, ...fibroblast cells surrounding the tumor express increased levels of
mRNA due to a decrease of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter activity. Little is known about the effects of environmental chemicals on the promoter-specific
expression.
We aimed to determine the effects of two neonicotinoids (thiacloprid and imidacloprid) on promoter-specific
expression in Hs578t breast cancer cells and understand the signaling pathways involved.
Hs578t cells were exposed to various signaling pathway stimulants or neonicotinoids for 24 h. Promoter-specific expression of
was determined by real-time quantitative polymerase chain reaction and catalytic activity of aromatase by tritiated water release assay.
To our knowledge, we are the first to demonstrate that the normal I.4 promoter and the breast cancer-relevant PII, I.3, and I.7 promoters of
are active in these cells. We found that the expression of
via promoters PII, I.3, and I.7 in Hs578t cells was, in part, dependent on the activation of two VEGF signaling pathways: mitogen-activated protein kinase (MAPK) 1/3 and phospholipase C (PLC). Exposure of Hs578t cells to environmental concentrations of imidacloprid and thiacloprid resulted in a switch in
promoter usage, involving inhibition of I.4 promoter activity and an increase of PII, I.3, and I.7 promoter-mediated
expression and aromatase catalytic activity. Greater effects were seen at lower concentrations. Our results suggest that thiacloprid and imidacloprid exert their effects at least partially by inducing the MAPK 1/3 and/or PLC pathways.
We demonstrated
that neonicotinoids may stimulate a change in
promoter usage similar to that observed in patients with hormone-dependent breast cancer. https://doi.org/10.1289/EHP2698.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, IZUM, KILJ, NUK, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
This study investigated the occurrence of a comprehensive suite of polybrominated diphenyl ethers (PBDEs) and current-use flame retardants (FRs) in ring-billed gulls breeding in a highly ...industrialized section of the St. Lawrence River, downstream from Montreal (QC, Canada). Despite major point-sources and diffuse contamination by FRs, nearly no FR data have been reported in birds from this area. Bis(2-ethylhexyl)-2,3,4,5-tetrabromophthalate (BEHTBP) was detected in 89% of ring-billed gull livers (mean: 2.16 ng/g ww; max: 17.6 ng/g ww). To our knowledge, this is the highest detection frequency and highest concentrations reported thus far in any avian species or populations. Dechlorane Plus (DP) isomers were also particularly abundant (anti-DP detected in 100% and syn-DP in 93% of livers). Other detected FR compounds (3–14% detection) included 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (EHTBB), hexachlorocyclopentenyl-dibromocyclooctane (HCDBCO) and β-1,2-dibromo-4-(1.2-dibromoethyl)-cyclohexane (β-TBECH). Mean BDE-209 (57.2 ± 12.2 ng/g ww) in ring-billed gull livers was unexpectedly high for this midtrophic gull species, exceeding levels reported in several apex raptors such as peregrine falcons. BDE-209’s relative contribution to ∑PBDEs was on average 25% (exceeding BDE-47 and BDE-99) and contrasted with profiles typically reported for fish-eating gull species. The present study highlighted preoccupying gaps in upcoming FR regulations and stressed the need for further investigation of the sources of FR exposure in highly urbanized areas.
•A PFAS mixture was examined in association with cardiometabolic health in Nunavik.•PFAS were associated with increases in lipoproteins and prediabetes.•No associations were observed with diabetes ...and high blood pressure.
The cardiometabolic health status of Inuit in Nunavik has worsened in the last thirty years. The high concentrations of perfluoroalkyl acids (PFAAs) may be contributing to this since PFAAs have been linked with hypercholesterolemia, diabetes, and high blood pressure. The aim of this study was to examine the association between a PFAAs mixture and lipid profiles, Type II diabetes, prediabetes, and high blood pressure in this Inuit population.
We included 1212 participants of the Qanuilirpitaa? 2017 survey aged 16–80 years. Two mixture models (quantile g-computation and Bayesian Kernel Machine Regression (BKMR)) were used to investigate the associations between six PFAAs (PFHxS, PFOS, PFOA and three long-chain PFAAs (PFNA, PFDA and PFUnDA)) with five lipid profiles and three cardiometabolic outcomes. Non-linearity and interaction between PFAAs were further assessed.
An IQR increase in all PFAAs congeners resulted in an increase in total cholesterol (β 0.15, 95% confidence interval (CI) 0.06, 0.24), low-density lipoprotein cholesterol (LDL) (β 0.08, 95% CI 0.01, 0.16), high-density lipoprotein cholesterol (HDL) (β 0.04, 95% CI 0.002, 0.08), apolipoprotein B-100 (β 0.03, 95% CI 0.004, 0.05), and prediabetes (OR 1.80, 95% CI 1.11, 2.91). There was no association between PFAAs and triglycerides, diabetes, or high blood pressure. Long-chain PFAAs congeners were the main contributors driving the associations. Associations were largely linear, and there was no evidence of interaction between the PFAAs congeners.
Our study provides further evidence of increasing circulating lipids with increased exposure to PFAAs. The increased risk of prediabetes points to the influence of PFAAs on potential clinical outcomes. International regulation of PFAAs is essential to curb PFAAs exposure and related health effects in Arctic communities.
Serum composition of PFAAs congeners in Nunavik pregnant women from the NQN study in 2016–2017 compared to women from the Canadian general population who participated in the Canadian Health Measure ...Survey (CHMS) cycle 5.
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•In pregnant women from Nunavik, exposure to long-chain PFAAs is increasing.•Nunavimmiut women exposure to PFOS, PFNA, PFDA and PFuDA was higher than in the Canadian general population.•The results suggest that 8:2 FTOH contributes to the exposure profile in the Arctic.•Marine country food consumption is associated with higher exposure to PFAAs.
Perfluoroalkyl acids (PFAAs) are persistent and ubiquitous environmental contaminants that potentially disrupt endocrine system functions. While some PFAAs (perfluorooctane sulfonate (PFOS), perfluorooctanoic acid (PFOA)) are regulated, currently used fluorotelomer alcohols (FTOHs) can be transported to the Arctic and are degraded in a number of PFAAs which biomagnify in Arctic wildlife (e.g. perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUdA)).
From 2004 to 2017, 279 pregnant Inuit women were recruited as part of biomonitoring projects in Nunavik. Our goal was to evaluate: (i) time-trends in plasma/serum PFAAs levels in pregnant Nunavimmiut women between 2004 and 2017; (ii) compare plasma/serum PFAAs levels in Nunavimmiut women in 2016–2017 to those measured in women of childbearing age in the Canadian Health Measure Survey (CHMS); and (iii) evaluate the associations of PFAAs levels with the consumption of country foods and pregnancy and maternal characteristics during pregnancy in the 97 participants recruited in 2016–2017.
Individual blood sample were collected for serum or plasma PFAAs (PFOS, PFOA, pentafluorobenzoic acid (PFBA), perfluorohexanoic acid (PFHxA), perfluorobutanesulfonic acid (PFBS), perfluorohexane-1-sulfonic acid (PFHxS), PFNA, PFDA, PFUdA) analyses. Socio-demographic data, pregnancy and maternal characteristics and country foods consumption were documented using a questionnaire. Omega-3 and −6 polyunsaturated fatty acids (PUFA) were measured in red blood cell membranes and their ratio used as a biomarker of marine country foods consumption. Time-trends in PFAAs levels were evaluated using ANCOVA models adjusted for relevant co-variables. Serum/plasma levels of PFAAs in the 97 pregnant women aged 16 to 40 years old and recruited in 2016–2017 were compared to those measured in women aged 18 to 40 years old from the CHMS cycle 5 (2016–2017) using the geometric means (GM) and 95% confidence intervals (95% CI). Multivariate regression analyses were performed to examine associations between concentrations of PFAAs and country foods consumption data.
Statistically-significant downward time trends were noted for concentrations of PFOS, PFOA and PFHxS in pregnant Nunavik women between 2004 and 2017. Conversely, between 2011 and 2016–2017, PFNA, PFDA and PFUdA maternal serum levels increased by 19, 13 and 21% respectively. Among participants in 2016–2017, mean concentrations for PFNA (GM: 2.4 μg/L), PFDA (0.53 μg/L) and PFUdA (0.61 μg/L) were higher than those measured in women aged 18–40 years old in the Cycle 5 (2016–2017) of the CHMS. PFOA (0.53 μg/L) and PFHxS (0.26 μg/L) were lower than in CHMS, whereas PFBA, PFHxA and PFBS were not detected in 2016–2017. Ratios of serum/plasma levels of PFNA/PFOA, PFNA/PFOS, PFNA/PFHxS and PFUdA/PFDA were significantly higher in the 97 pregnant women from Nunavik recruited in 2016–2017 compared to CHMS, highlighting their distinct exposure profile. In multivariate models, PFHxS, PFOS, PFNA, PFDA and PFUdA levels in 2016–2017 were strongly associated with the omega-3/omega-6 PUFA ratio, indicating a positive association between marine country foods consumption and higher exposure to PFAAs.
The exposure of pregnant women to long-chain PFAAs (PFNA, PFDA and PFUdA) increased from 2004 to 2017 in Nunavik. Associations noted between PFAAs levels and the omega-3/omega-6 ratio highlights the importance of implementing additional strict regulations on PFAAs and their precursors to protect the high nutritional quality and cultural importance of country foods in Nunavik.
Perfluoroalkyl substances (PFASs) are found in several consumer goods. Exposure to PFASs in children has been associated with alteration in thyroid hormones, which have critical roles in brain ...function.
In 2015, 198 children and youth (3–19 y) were recruited as part of the pilot project Jeunes, Environnement et Santé/Youth, Environment and Health (JES!-YEH!), realized in collaboration with four First Nation communities in Quebec. We aimed to evaluate serum concentrations of PFASs in relation to concentrations of thyroid-stimulating hormone (TSH), free thyroxine (T4) and thyroglobulin while adjusting for relevant confounders.
PFASs (PFOS, PFOA, PFHxS, PFNA), 2,2′,4,4′-Tetrabromodiphenyl ether (PBDE-47) thyroid parameters (TSH, free T4, and thyroglobulin) were measured in serum samples of 186 participants. Iodine, creatinine, and cotinine were measured in urine samples. Serum levels of PFASs were compared to those measured in the general Canadian population and elsewhere. Multivariate regression analyses were performed to determine associations between PFASs and TSH, free T4 and thyroglobulin.
PFOS, PFOA and PFHxS serum concentrations were low. However, PFNA concentrations among participants aged 12 to 19 years old from Anishinabe communities were three times higher than those measured in the Canadian Health Measures Survey (2009–2011) for the same age group (Geometric Means: 3.01 μg/L and 0.71 μg/L, respectively) and were particularly higher in the Anishinabe participants aged 6 to 11 years old (GM: 9.44 μg/L). Few participants had levels of TSH, free T4, and thyroglobulin outside age-specific paediatric ranges. When adjusted for relevant covariates and other contaminants, PFNA serum concentrations were positively associated with free T4 levels (Adjusted β = 0.36; p = 0.0014), but not with TSH and thyroglobulin levels. No association was observed between the other PFAS and thyroid hormones parameters.
This pilot project reveals among the highest exposure to PFNA in children reported until today, and suggests effects of PFNA as an endocrine disruptor, highlighting the importance of investigating the sources and effects of disproportionate exposure to emerging contaminants in some indigenous communities and ban all PFAS at the international scale.
•Serum PFOS, PFOA, PFHxS and PFNA were measured in 186 children from four First Nations communities in Quebec.•PFNA exposure among Anishinabe participants was among the highest reported to date in children and youth.•Free T4 were positively associated with PFNA concentrations in adjusted models.•International actions to include all PFAS in the Stockholm Convention are urgently needed.
Hydraulic fracturing, a method used in Northeastern British Columbia (Canada) to extract natural gas, can release contaminants with potential deleterious health effects on fetal development. To date, ...the association between hydraulic fracturing activity and birth outcomes has not been evaluated in this region.
To evaluate the association between the hydraulic fracturing well density/proximity and birth outcomes (birthweight, head circumference, preterm birth and small for gestational age (SGA)).
We used birth records from the Fort St John hospital between December 30, 2006 and December 29, 2016 (n = 6333 births). To estimate gestational exposure, we used inverse distance weighting (IDW) to calculate the density/proximity of hydraulic fracturing wells to pregnant women's postal code centroid. For each birth, we calculated three IDWs using 2.5, 5, and 10 km buffer zones around women's postal code centroid. We used linear and logistic regressions to evaluate associations between quartiles of postal code well density/proximity and birth outcomes, controlling for relevant covariates.
No associations were found between postal code well density/proximity and head circumference or SGA. A negative association was found between postal code well density/proximity and birthweight for infants born to women in the 2nd quartile of the 10 km buffer (β 95% confidence interval (CI): -47.28 g -84.30; -10.25), and in the 2nd (β 95% CI: -40.87 g -78.01; -3.73) and 3rd (β 95% CI: -42.01 g -79.15; -4.87) quartiles of the 5 km buffer. Increased odds of preterm birth were observed among women in the 2nd quartile of the 2.5 km buffer (odds ratio (OR) 95% CI: 1.60 1.30; 2.43).
This is the first epidemiological study in Northeastern British Columbia evaluating associations between hydraulic fracturing and health outcomes. Our results show inconsistent patterns of association between hydraulic fracturing, preterm birth and reduced birthweight, and effect estimates did not match expected dose-response relationships.
Perfluoroalkyl acids (PFAAs), a subset of perfluoroalkyl substances (PFAS), are synthetic chemicals used in industrial and consumer applications. They are exceptionally stable and highly mobile in ...the environment, and were detected in high concentrations in Arctic wildlife and Nunavik Inuit. The study's objective was to study the association between dietary profiles in Nunavik and plasma PFAAs concentrations.
The study used data from the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) (N = 1172) on Inuit adults aged 16–80 years. Nine PFAAs congeners were measured in plasma samples (six were detected). Dietary profiles were identified using latent profile analysis. Two sets of dietary profiles were included; the first included market (store-bought) and country foods (harvested/hunted from the land), and the second included only country foods. Multiple linear regression models regressed log-transformed PFAAs concentrations against the dietary profiles, adjusting for sociodemographic variables.
We identified statistically significant 24.54–57.55 % increases in all PFAAs congeners (PFOA, PFNA, PFDA, PFUnDA, PFHxS, and PFOS) in the dietary profile defined by frequent country food consumption compared to the dietary profile defined by frequent market food consumption. Individuals defined by low consumption of foods (related to food insecurity) had higher concentrations of six PFAAs compared to individuals with frequent market food consumption. The associations were stronger with profiles defined by more frequent country food consumption, and particularly those with increased marine mammal consumption. PFDA, PFUnDA, and PFOS were particularly associated with high country food consumption frequency, such that their concentrations increased by approximately 67–83 % compared to those reporting no or very little consumption of any country foods.
Increased country food consumption was strongly associated with higher PFAAs concentrations, particularly PFOS, PFDA, and PFUnDA. The results provide further evidence that the quality of country foods is being threatened by PFAAs contamination. Additional national and international regulations are required to protect the Arctic and its inhabitants from these pollutants.
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•High concentrations of environmentally persistent perfluoroalkyl acids (PFAAs) were detected in Inuit populations.•We examined associations between dietary profiles and PFAAs concentrations using data from a large survey in Nunavik.•The strongest associations were between food profiles with frequent country food consumption and long-chain PFAAs.•Dietary profiles with frequent consumption of marine mammals were also associated with higher concentrations of PFAAs.•These results provide evidence for country foods as an exposure source of PFAAs in Arctic communities.
Halogenated organophosphate esters (OPEs) are increasingly used as flame retardants to replace polybrominated diphenyl ethers (PBDEs), which have been phased out due to their confirmed persistence, ...toxicity, and ability to undergo long range atmospheric transport. Non-halogenated OPEs are primarily used as plasticizers. While human exposure to PBDEs in the Canadian Arctic is well documented, it is not the case for OPEs. To assess the exposure to OPEs in Inuit living in Nunavik (northern Québec, Canada), we measured 16 metabolites of halogenated and non-halogenated OPEs in pooled urine samples from the last population health survey conducted in Nunavik, the Qanuilirpitaa? 2017 Inuit Health Survey (Q2017). Urine samples (n = 1266) were pooled into 30 pools by sex (female; male), age groups (16–19; 20–29; 30–39; 40–59; 60+ years old) and regions (Hudson Bay; Hudson Strait; Ungava Bay). Q2017 geometric means and 95 % confidence intervals were compared with data from the Canadian Health Measures Survey Cycle 6 (2018–2019) (CHMS). Halogenated OPEs were systematically detected and generally found at higher concentrations than non-halogenated OPEs in both Q2017 and CHMS. Furthermore, urinary levels of BCIPP and BDCIPP (halogenated) were lower in Q2017 compared to CHMS while concentrations of DPhP, DpCP and DoCP (non-halogenated) were similar between Q2017 and CHMS. Across the 16 metabolites measured in Q2017, BCIPHIPP (halogenated) had the highest levels (geometric mean: 1.40 μg/g creatinine). This metabolite was not measured in CHMS and should be included in future surveys. Overall, our results show that Inuit in Nunavik are exposed to lower or similar OPEs levels than the rest of the general Canadian population suggesting that the main current exposure to OPEs may be from consumer goods containing flame retardants and imported from the south rather than long-range atmospheric transport to the Arctic.
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•16 OPE urinary metabolites were measured in people 16y and older from Nunavik (Nunavimmiut).•OPE metabolite levels in Nunavimmiut are similar or lower than the Canadian general population.•This is the first biomonitoring study of OPE metabolites in Nunavimmiut.
Persistent organic pollutant exposures are well-documented in the Arctic, but fewer studies examined non-persistent chemicals, despite increased market food and consumer product consumption.
To ...measure phenol, paraben, phthalate, and alternative plasticizer concentrations in Inuit adults.
The study included 30 pooled urine samples from Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017) participants. Creatinine-adjusted geometric mean concentrations (GM) and 95% confidence intervals (CI) were compared across sex, age, and regions, and compared to those in the Canadian Health Measures Survey (CHMS) and the First Nations Biomonitoring Initiative (FNBI).
Q2017 bisphenol-A concentrations were double the CHMS 2018-2019 concentrations GM (95% CI): 1.98 (1.69-2.31) versus 0.71 (0.60-0.84) µg/g creatinine, but in line with FNBI 1.74 (1.41-2.13) µg/g creatinine. Several phthalate concentrations were higher in Q2017 versus CHMS, particularly monobenzyl phthalate, which was was 19-fold higher in Q2017 versus CHMS 2018-2019 45.26 (39.35-52.06) versus 2.4 (2.0-2.9) µg/g creatinine and four-fold higher than FNBI. There were also four-fold higher concentrations of the two alternate plasticizer 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TIXB) metabolites in Q2017 compared to CHMS 2018-2019. Women and people living in Ungava Bay had generally higher concentrations of non-persistent chemicals.
The results suggest higher concentrations of certain non-persistent chemicals in Inuit versus the general Canadian population.
Few studies have explored non-persistent chemical distributions in Northern communities, despite the increasing consumer product and market food consumption. We analyzed 30 pooled samples from the Qanuilirpitaa? Nunavik Inuit Health Survey 2017 to assess exposures to common plasticizes and plastic constituents and compare their levels with the general Canadian population and First Nation groups. We observed particularly higher levels of bisphenol-A, of monobenzyl phthalate, and of two 2,2,4-trimethyl-1,3-pentanediol diisobutyrate (TXIB) metabolites among Nunavimmiut compared to the general Canadian population, notably among women and Ungava Bay residents. Larger studies are required to confirm our findings and identify potential adverse health effects from these exposures.
Despite the growing unconventional natural gas production industry in northeastern British Columbia, Canada, few studies have explored the air quality implications on human health in nearby ...communities. Researchers who have worked with pregnant women in this area have found higher levels of volatile organic compounds (VOCs) in the indoor air of their homes associated with higher density and closer proximity to gas wells. To inform ongoing exposure assessments, this study develops land use regression (LUR) models to predict ambient air pollution at the homes of pregnant women by using natural gas production activities as predictor variables. Using the existing monitoring network, the models were developed for three temporal scales for 12 air pollutants. The models predicting monthly, bi-annual, and annual mean concentrations explained 23%–94%, 54%–94%, and 73%–91% of the variability in air pollutant concentrations, respectively. These models can be used to investigate associations between prenatal exposure to air pollutants associated with natural gas production and adverse health outcomes in northeastern British Columbia.
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•Assessing exposure to hydraulic fracturing is hindered by sparse air quality monitors.•Developed LUR models using air quality data and oil and gas production data.•Used LUR models to predict ambient air pollution concentrations.•Concentrations can be used to assess health outcomes and environmental justice.
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