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Maertens R.M.,Healthy Environmental | White P.A.,Healthy Environmental | Williams A.,Healthy Environmental | Yauk C.L.,Healthy Environmental
Toxicology | Year: 2013

Like tobacco smoking, habitual marijuana smoking causes numerous adverse pulmonary effects. However, the mechanisms of action involved, especially as compared to tobacco smoke, are still unclear. To uncover putative modes of action, this study employed a toxicogenomics approach to compare the toxicological pathways perturbed following exposure to marijuana and tobacco smoke condensate in vitro. Condensates of mainstream smoke from hand-rolled tobacco and marijuana cigarettes were similarly prepared using identical smoking conditions. Murine lung epithelial cells were exposed to low, medium and high concentrations of the smoke condensates for 6. h. RNA was extracted immediately or after a 4. h recovery period and hybridized to mouse whole genome microarrays. Tobacco smoke condensate (TSC) exposure was associated with changes in xenobiotic metabolism, oxidative stress, inflammation, and DNA damage response. These same pathways were also significantly affected following marijuana smoke condensate (MSC) exposure. Although the effects of the condensates were largely similar, dose-response analysis indicates that the MSC is substantially more potent than TSC. In addition, steroid biosynthesis, apoptosis, and inflammation pathways were more significantly affected following MSC exposure, whereas M phase cell cycle pathways were more significantly affected following TSC exposure. MSC exposure also appeared to elicit more severe oxidative stress than TSC exposure, which may account for the greater cytotoxicity of MSC. This study shows that in general MSC impacts many of the same molecular processes as TSC. However, subtle pathway differences can provide insight into the differential toxicities of the two complex mixtures. © 2013.

Nguyen K.C.,Healthy Environmental | Nguyen K.C.,Carleton University | Willmore W.G.,Carleton University | Tayabali A.F.,Healthy Environmental
Toxicology | Year: 2013

The mechanisms of toxicity related to human hepatocellular carcinoma HepG2 cell exposures to cadmium telluride quantum dots (CdTe-QDs) were investigated. CdTe-QDs caused cytotoxicity in HepG2 cells in a dose- and time-dependent manner. Treated cells showed an increase in reactive oxygen species (ROS). Altered antioxidant levels were demonstrated by depletion of reduced glutathione (GSH), a decreased ratio of reduced glutathione to oxidized glutathione (GSH/GSSG) and an increased NF-E2-related Factor 2 (Nrf2) activation. Enzyme assays showed that superoxide dismutase (SOD) activity was elevated whereas catalase (CAT) and glutathione-S-transferase (GST) activities were depressed. Further analyses revealed that CdTe-QD exposure resulted in apoptosis, indicated by changes in levels of caspase-3 activity, poly ADP-ribose polymerase (PARP) cleavage and phosphatidylserine externalization. Extrinsic apoptotic pathway markers such as Fas levels and caspase-8 activity increased as a result of CdTe-QD exposure. Involvement of the intrinsic/mitochondrial apoptotic pathway was indicated by decreased levels of B-cell lymphoma 2 (Bcl2) protein and mitochondrial cytochrome c, and by increased levels of mitochondrial Bcl-2-associated X protein (Bax) and cytosolic cytochrome c. Further, mitogen-activated protein kinases (MAPKs) such as c-Jun N-terminal kinases (JNK), extracellular signal-regulated kinases (Erk1/2), and p38 were all activated. Our findings reveal that CdTe-QDs cause oxidative stress, interfere with antioxidant defenses and activate protein kinases, leading to apoptosis via both extrinsic and intrinsic pathways. Since the effects of CdTe-QDs on selected biomarkers were similar or greater compared to those of CdCl2 at equivalent concentrations of cadmium, the study suggests that the toxicity of CdTe-QDs arises from a combination of the effects of cadmium and ROS generated from the NPs. © 2013.

Dong H.,Healthy Environmental | Wade M.G.,Healthy Environmental
Toxicology in Vitro | Year: 2017

Thyroid hormones (THs) play important roles in almost all physiological processes. High-throughput screening (HTS) assays are needed to screen the vast numbers of chemicals for their potential to disrupt TH signalling. The current work has confirmed the ability of a rapid assay to identify substances inhibiting TH uptake through monocarboxylate transporter (MCT) 8. Perturbation of MCT8 function results in significant developmental impairments, suggesting substances inhibiting MCT8 may be important developmental toxicants. We examined the accuracy and consistency of a recently described method to identify TH inhibitors via MCT8, using MDCK cells overexpressing human MCT8 gene. We confirmed the method detected T3 uptake in a concentration/time-dependent manner, and this effect was blocked by substances previous reported to block TH uptake via MCT8. Assay performance was assessed extensively and the system was found to have high signal dynamic range and Z’ factor. The assay was also validated with a diverse set of training chemicals. This assay was then used to screen chemicals suspected to disrupt TH signalling. Other than bisphenol A (BPA), all substances tested were negative. Our results suggest that this assay could be part of a battery of screening assays to predict the potential thyroid disrupting activity of chemicals. © 2017

Freeland A.L.,Centers for Disease Control and Prevention | Banerjee S.N.,National Center for Environmental Health | Dannenberg A.L.,Healthy Environmental | Wendel A.M.,Healthy Environmental
American Journal of Public Health | Year: 2013

Objectives. We assessed changes in transit-associated walking in the United States from 2001 to 2009 and documented their importance to public health. Methods. We examined transit walk times using the National Household Travel Survey, a telephone survey administered by the US Department of Transportation to examine travel behavior in the United States. Results. People are more likely to transit walk if they are from lower income households, are non-White, and live in large urban areas with access to rail systems. Transit walkers in large urban areas with a rail system were 72% more likely to transit walk 30 minutes or more per day than were those without a rail system. From 2001 to 2009, the estimated number of transit walkers rose from 7.5 million to 9.6 million (a 28% increase); those whose transit-associated walking time was 30 minutes or more increased from approximately 2.6 million to 3.4 million (a 31% increase). Conclusions. Transit walking contributes to meeting physical activity recommendations. Study results may contribute to transportation-related health impact assessment studies evaluating the impact of proposed transit systems on physical activity, potentially influencing transportation planning decisions.

Boothe V.L.,Scientific-Atlanta | Boehmer T.K.,National Center for Environmental Health | Wendel A.M.,Healthy Environmental | Yip F.Y.,National Center for Environmental Health
American Journal of Preventive Medicine | Year: 2014

Context Exposure to elevated concentrations of traffic-related air pollutants in the near-road environment is associated with numerous adverse human health effects, including childhood cancer, which has been increasing since 1975. Results of individual epidemiologic studies have been inconsistent. Therefore, a meta-analysis was performed to examine the association between residential traffic exposure and childhood cancer. Evidence acquisition Studies published between January 1980 and July 2011 were retrieved from a systematic search of 18 bibliographic databases. Nine studies meeting the inclusion criteria were identified. Weighted summary ORs were calculated using a random effects model for outcomes with four or more studies. Subgroup and sensitivity analyses were performed. Evidence synthesis Childhood leukemia was positively associated (summary OR=1.53, 95% CI=1.12, 2.10) with residential traffic exposure among seven studies using a postnatal exposure window (e.g., childhood period or diagnosis address) and there was no association (summary OR=0.92, 95% CI=0.78, 1.09) among four studies using a prenatal exposure window (e.g., pregnancy period or birth address). There were too few studies to analyze other childhood cancer outcomes. Conclusions Current evidence suggests that childhood leukemia is associated with residential traffic exposure during the postnatal period, but not during the prenatal period. Additional well-designed epidemiologic studies that use complete residential history to estimate traffic exposure, examine leukemia subtypes, and control for potential confounding factors are needed to confirm these findings. As many people reside near busy roads, especially in urban areas, precautionary public health messages and interventions designed to reduce population exposure to traffic might be warranted. © 2014 American Journal of Preventive Medicine.

Haines D.A.,Healthy Environmental | Murray J.,Healthy Environmental
International Journal of Hygiene and Environmental Health | Year: 2012

Human biomonitoring is an important indicator and measure of exposure to environmental chemicals and provides information to support health protection policies and programs. Cycle 1 (2007-2009) of the Canadian Health Measures Survey (CHMS) collected and analyzed biological samples from over 5600 males and females aged 6-79 years, which established national representative blood and urine concentrations for a number of environmental chemicals including metals, organophosphate insecticide metabolites, polychlorinated biphenyls (PCBs), organochlorines (OCs), perfluorinated compounds (PFCs), bisphenol A (BPA), and cotinine. The results of CHMS Cycle 1 indicate that while some organophosphate insecticide metabolites were below limits of detection for most participants, metals, PCBs, OCs, PFCs and BPA were detected in almost all blood or urine samples. Significant differences (p< 0.05) in blood concentrations between males and females were also determined for several metals (e.g., lead for males and females was 15.1 and 11.8μg/L, respectively), PFCs (e.g., PFOS for males and females was 11.13 and 7.07μg/L, respectively), and OCs (e.g., p,p'-DDE for males and females was 134.43 and 172.07μg/kg lipid, respectively) and in urine concentrations for BPA (1.29 and 1.04μg/L for males and females, respectively). Future cycles of the CHMS will permit temporal trend analysis for a number of these chemicals. © 2011.

Gavina J.M.A.,Healthy Environmental | Yao C.,Healthy Environmental | Feng Y.-L.,Healthy Environmental
Talanta | Year: 2014

DNA adducts represent an important category of biomarkers for detection and exposure surveillance of potential carcinogenic and genotoxic chemicals in the environment. Sensitive and specific analytical methods are required to detect and differentiate low levels of adducts from native DNA from in vivo exposure. In addition to biomonitoring of environmental pollutants, analytical methods have been developed for structural identification of adducts which provides fundamental information for determining the toxic pathway of hazardous chemicals. In order to achieve the required sensitivity, mass spectrometry has been increasingly utilized to quantify adducts at low levels as well as to obtain structural information. Furthermore, separation techniques such as chromatography and capillary electrophoresis can be coupled to mass spectrometry to increase the selectivity. This review will provide an overview of advances in detection of adducted and modified DNA by mass spectrometry with a focus on the analysis of nucleosides since 2007. Instrument advances, sample and instrument considerations, and recent applications will be summarized in the context of hazard assessment. Finally, advances in biomonitoring applying mass spectrometry will be highlighted. Most importantly, the usefulness of DNA adducts measurement and detection will be comprehensively discussed as a tool for assessment of in vitro and in vivo exposure to environmental pollutants. © 2014 Published by Elsevier B.V. All rights reserved.

Miyata R.,University of British Columbia | Bai N.,University of British Columbia | Vincent R.,Healthy Environmental | Sin D.D.,University of British Columbia | Van Eeden S.F.,University of British Columbia
Chest | Year: 2013

Background: The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) suppress ambient particulate matter , 10 m m (PM 10 )-induced infl ammatory response in vitro. The aim of this study was to determine the effect of statins on PM 10 -induced lung infl ammation in vivo. Methods: New Zealand white rabbits were exposed to either PM 10 (1.0 mg/kg) or saline by direct intratracheal instillation three times a week for 4 weeks - lovastatin 5.0 mg/kg/d. BAL fluid was assessed for cell counts and proinfl ammatory cytokine levels. Lung infl ammation was quantifi ed using immunohistochemical techniques and morphometric methods. Ex vivo phagocytosis assay of alveolar macrophages using PM 10 particles was performed. Distribution of PM 10 particles in lung tissues and draining lymph nodes was quantifi ed morphometrically to evaluate the clearance of PM 10 particles. Results: PM 10 exposure increased the production of IL-6 and IL-8, promoted the recruitment of macrophages and polymorphonuclear leukocytes into the lung, and activated these recruited leukocytes. Lovastatin signifi cantly suppressed all these effects. Lovastatin increased the phagocytic activity of macrophages and promoted the migration of PM 10 -laden macrophages to the regional lymph nodes. Conclusions: Lovastatin attenuates the PM 10 -induced recruitment and activation of alveolar macrophages and polymorphonuclear leukocytes, reduces local proinfl ammatory cytokine production, and promotes the clearance of PM 10 particles from lung tissues to regional lymph nodes. These novel pleiotropic properties of statins are most likely to contribute to the downregulation of PM 10 -induced lung infl ammation. CHEST 2013; 143(2):452-460 © 2013 American College of Chest Physicians.

Kubwabo C.,Healthy Environmental | Fan X.,Healthy Environmental | Rasmussen P.E.,Healthy Environmental | Wu F.,Healthy Environmental
Analytical and Bioanalytical Chemistry | Year: 2012

A new method for the simultaneous determination of 11 synthetic musks and one fragrance compound in house dust was developed. The nitro musks included musk ketone (MK, 4-tert-butyl-3,5-dinitro-2,6-dimethylacetophenone), musk xylene (MX, 1-tert-butyl-3,5-dimethyl-2,4,6- trinitrobenzene), musk ambrette (1-tert-butyl-2-methoxy-4- methyl-3,5-dinitrobenzene) and musk moskene (1,1,3,3, 5-pentamethyl-4,6-dinitroindane). The polycyclic musk compounds were 1,3,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-( ?)-2-benzopyran (HHCB), 7-acetyl- 1,1,3,4,4,6-hexamethyl-1,2,3,4-tetrahydronaphthalene (AHTN), 4-acetyl-1,1-dimethyl-6-tert-butylindane, 6- acetyl-1,1,2,3,3,5- hexamethylindane, 5-acetyl-1,1,2,6-tetramethyl- 3-isopropylindane, 6,7-dihydro-1,1,2,3,3-pentamethyl- 4(5H)-indanon. The one macrocyclic musk was 1,4-dioxacycloheptadecane-5,17-dione. The bicyclic hydrocarbon fragrance compound (1,2,3,4,5,6,7,8-octahydro- 2,3,8,8-tetramethylnaphthalen-2yl)ethan-1- one (OTNE) and HHCB- l a c t o n e ( 4 , 6 , 6 , 7 , 8 , 8 -hexame t h y l - 1H,3H,4H,6H,7H, 8H-indeno[5,6-c]pyran-1-one), a degradation product of HHCB, were also analysed. NIST SRM 2781 (domestic sludge) and SRM 2585 (organic contaminants in house dust) were analysed for these target compounds. The method was applied for the analysis of 49 paired samples collected using two vacuum sampling methods: a sample of fresh or "active" dust (FD) collected using a Pullman-Holt vacuum sampler, and a household dust (HD) sample taken from the participants' vacuum cleaners. Method detection limits and recoveries ranged from 12 to 48 ng/g and 54 to 117 %, respectively. AHTN, HHCB, OTNE and HHCB-lactone were detected in all samples, with median concentrations of 552, 676, 252 and 453 ng/g for FD samples, respectively; and 405, 992, 212 and 492 ng/g for HD samples, respectively. MX and MK were detected with high frequencies but with much lower concentrations. The two sampling methods produced comparable results for the target analytes. Widely scattered concentration levels were observed for target analytes from this set of 49 house dust samples, suggesting a wide variability in Canadian household exposure to synthetic musks. © Springer-Verlag 2012.

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