13 research outputs found
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Assessment of chlorinated pesticides and polychlorinated biphenyls in adipose breast tissue using a supercritical fluid extraction method
A precise and highly reproducible analytical method was developed for the assessment of organochlorinated pesticide and polychlorinated biphenyl residues in adipose tissue (> or = 50 mg). The method can be utilized for epidemiological studies on the significance of these environmental pollutants in the etiology of breast cancer. Supercritical fluid extraction (SFE) with CO2 and modified CO2 (addition of 5% dichloromethane) is employed to remove incurred pesticide residues from adipose tissues that have been surgically removed from breast cancer patients and controls. An alumina sorbent, placed in the extracting vessel together with a specimen, removes the bulk of co-extracted lipids; a subsequent purification of the SFE extracts by column chromatography on alumina removes the remaining traces of lipids that would interfere with the gas chromatographic analysis with electron capture detection. The method was tested by analyzing a Certified Reference Material 430 pork fat with known amounts of pesticide residues that are commonly found in fat or in foods with a high fat content. The recoveries of analytes ranged from 73.4% for endrin to 115% for alpha-, beta- and gamma-hexachlorocyclohexane, hexachlorobenzene and dieldrin, with standard deviations of 4-12% for individual analytes. The analysis of adipose tissue for organochlorinated compounds on the basis of this new method suggested that the pesticide levels were higher in breast cancer patients than in controls. However, the small number of samples analyzed in this study (n = 5, both groups) precludes definitive conclusions. The most abundant compounds in both cases and controls were p, p-DDE (379 +/- 286 and 160 +/- 149 p.p.b.) and PCB (223 +/- 145 and 124 +/- 65.7 p.p.b.), followed by the termiticide chlordane residues oxychlordane and transnonachlor
Validation and Calibration of a Model Used to Reconstruct Historical Exposure to Polycyclic Aromatic Hydrocarbons for Use in Epidemiologic Studies
OBJECTIVES: We previously developed a historical reconstruction model to estimate exposure to airborne polycyclic aromatic hydrocarbons (PAHs) from traffic back to 1960 for use in caseācontrol studies of breast cancer risk. Here we report the results of four exercises to validate and calibrate the model. METHODS: Model predictions of benzo[a]pyrene (BaP) concentration in soil and carpet dust were tested against measurements collected at subjectsā homes at interview. In addition, predictions of air intake of BaP were compared with blood PAHāDNA adducts. These same soil, carpet, and blood measurements were used for model optimization. In a separate test of the meteorological dispersion part of the model, predictions of hourly concentrations of carbon monoxide from traffic were compared with data collected at a U.S. Environmental Protection Agency monitoring station. RESULTS: The data for soil, PAHāDNA adducts, and carbon monoxide concentrations were all consistent with model predictions. The carpet dust data were inconsistent, suggesting possible spatial confounding with PAH-containing contamination tracked in from outdoors or unmodeled cooking sources. BaP was found proportional to other PAHs in our soil and dust data, making it reasonable to use BaP historical data as a surrogate for other PAHs. Road intersections contributed 40ā80% of both total emissions and average exposures, suggesting that the repertoire of simple markers of exposure, such as traffic counts and/or distance to nearest road, needs to be expanded to include distance to nearest intersection
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Residential Environmental Exposures and other Characteristics Associated with Detectable PAH-DNA Adducts in Peripheral Mononuclear Cells in a Population-Based Sample of Adult Females
The detection of polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lymphocytes may be useful as a surrogate end point for individual cancer risk prediction. In this study, we examined the relationship between environmental sources of residential PAH, as well as other potential factors that may confound their association with cancer risk, and the detection of PAH-DNA adducts in a large population-based sample of adult women. Adult female residents of Long Island, New York, aged at least 20 years were identified from the general population between August 1996 and July 1997. Among 1556 women who completed a structured questionnaire, 941 donated sufficient blood (25+ ml) to allow use of a competitive ELISA for measurement of PAH-DNA adducts in peripheral blood mononuclear cells. Ambient PAH exposure at the current residence was estimated using geographic modeling (n=796). Environmental home samples of dust (n=356) and soil (n=360) were collected on a random subset of long-term residents (15+ years). Multivariable regression was conducted to obtain the best-fitting predictive models. Three separate models were constructed based on data from : (A) the questionnaire, including a dietary history; (B) environmental home samples; and (C) geographic modeling. Women who donated blood in summer and fall had increased odds of detectable PAH-DNA adducts (OR=2.65, 95% confidence interval (CI)=1.69, 4.17; OR=1.59, 95% CI=1.08, 2.32, respectively), as did current and past smokers (OR=1.50, 95% CI=1.00, 2.24; OR=1.46, 95% CI=1.05, 2.02, respectively). There were inconsistent associations between detectable PAH-DNA adducts and other known sources of residential PAH, such as grilled and smoked foods, or a summary measure of total dietary benzo-[a]-pyrene (BaP) intake during the year prior to the interview. Detectable PAH-DNA adducts were inversely associated with increased BaP levels in dust in the home, but positively associated with BaP levels in soil outside of the home, although CIs were wide. Ambient BaP estimates from the geographic model were not associated with detectable PAH-DNA adducts. These data suggest that PAH-DNA adducts detected in a population-based sample of adult women with ambient exposure levels reflect some key residential PAH exposure sources assessed in this study, such as cigarette smoking
Role of Peroxisome Proliferator-Activated Receptor Ī²/Ī“ and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells
PPARĪ²/Ī“ is a ligand-activated transcription factor that regulates various cellular functions via induction of target genes directly or in concert with its associated transcriptional repressor, BCL-6. Matrix remodeling proteinases are frequently over-expressed in pancreatic cancer and are involved with metastasis. The present study tested the hypothesis that PPARĪ²/Ī“ is expressed in human pancreatic cancer cells and that its activation could regulate MMP-9, decreasing cancer cells ability to transverse the basement membrane. In human pancreatic cancer tissue there was significantly higher expression of MMP-9 and PPARĪ²/Ī“, and lower levels of BCL-6 mRNA. PPARĪ²/Ī“ activation reduced the TNFĪ±-induced expression of various genes implicated in metastasis and reduced the invasion through a basement membrane in cell culture models. Through the use of short hairpin RNA inhibitors of PPARĪ²/Ī“, BCL-6, and MMP-9, it was evident that PPARĪ²/Ī“ was responsible for the ligand-dependent effects whereas BCL-6 dissociation upon GW501516 treatment was ultimately responsible for decreasing MMP-9 expression and hence invasion activity. These results suggest that PPARĪ²/Ī“ plays a role in regulating pancreatic cancer cell invasion through regulation of genes via ligand-dependent release of BCL-6 and that activation of the receptor may provide an alternative therapeutic method for controlling migration and metastasis
Highly reactive free radicals in electronic cigarette aerosols
Electronic cigarette (EC) usage has increased exponentially, but limited data are available on its potential harmful effects. We tested for the presence of reactive, short-lived free radicals in EC aerosols by electron paramagnetic resonance spectroscopy (EPR) using the spin-trap phenyl-N-tert-butylnitrone PBN. Radicals were detected in aerosols from all ECs and eliquids tested (2.5 Ć 10[exponent]13 to 10.3 Ć 10[exponent]13 radicals per puff at 3.3 V) and from eliquid solvents propylene glycol and glycerol and from "dry puffing". These results demonstrate, for the first time, the production of highly oxidizing free radicals from ECs which may present a potential toxicological risk to EC users