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"Environmental Pollutants - toxicity"
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Environmental chemicals, breast cancer progression and drug resistance
Breast cancer (BC) is one of the most common causes of cancer in the world and the second leading cause of cancer deaths among women. Mortality is associated mainly with the development of metastases. Identification of the mechanisms involved in metastasis formation is, therefore, a major public health issue. Among the proposed risk factors, chemical environment and pollution are increasingly suggested to have an effect on the signaling pathways involved in metastatic tumor cells emergence and progression. The purpose of this article is to summarize current knowledge about the role of environmental chemicals in breast cancer progression, metastasis formation and resistance to chemotherapy. Through a scoping review, we highlight the effects of a wide variety of environmental toxicants, including persistent organic pollutants and endocrine disruptors, on invasion mechanisms and metastatic processes in BC. We identified the epithelial-to-mesenchymal transition and cancer-stemness (the stem cell-like phenotype in tumors), two mechanisms suspected of playing key roles in the development of metastases and linked to chemoresistance, as potential targets of contaminants. We discuss then the recently described pro-migratory and pro-invasive Ah receptor signaling pathway and conclude that his role in BC progression is still controversial. In conclusion, although several pertinent pathways for the effects of xenobiotics have been identified, the mechanisms of actions for multiple other molecules remain to be established. The integral role of xenobiotics in the exposome in BC needs to be further explored through additional relevant epidemiological studies that can be extended to molecular mechanisms.
Journal Article
The fluorspar mines of Newfoundland : their history and the epidemic of radiation lung cancer
John Martin tells the history of Newfoundland's fluorspar mines from their founding to the last shipment of fluorspar in 1990 and declaration of bankruptcy a year later. He focuses on the health hazards experienced by the miners, and how the mining companies, workers, governments, and health services came to terms with the unfolding human tragedy. He also covers such matters as the improvement of methods for dust quantification and radiation surveillance in the mines, battles for compensation, and the influence of the St Lawrence case on the development of labour law in the province.
Book
Studying the Impact of Persistent Organic Pollutants Exposure on Human Health by Proteomic Analysis: A Systematic Review
Persistent organic pollutants (POPs) are organic chemical substances that are widely distributed in environments around the globe. POPs accumulate in living organisms and are found at high concentrations in the food chain. Humans are thus continuously exposed to these chemical substances, in which they exert hepatic, reproductive, developmental, behavioral, neurologic, endocrine, cardiovascular, and immunologic adverse health effects. However, considerable information is unknown regarding the mechanism by which POPs exert their adverse effects in humans, as well as the molecular and cellular responses involved. Data are notably lacking concerning the consequences of acute and chronic POP exposure on changes in gene expression, protein profile, and metabolic pathways. We conducted a systematic review to provide a synthesis of knowledge of POPs arising from proteomics-based research. The data source used for this review was PubMed. This study was carried out following the PRISMA guidelines. Of the 742 items originally identified, 89 were considered in the review. This review presents a comprehensive overview of the most recent research and available solutions to explore proteomics datasets to identify new features relevant to human health. Future perspectives in proteomics studies are discussed.
Journal Article
Endocrine Disrupting Chemicals: Current Understanding, New Testing Strategies and Future Research Needs
Endocrine disrupting chemicals (EDCs) are exogenous chemicals which can disrupt any action of the endocrine system, and are an important class of substances which play a role in the Developmental Origins of Health and Disease (DOHaD) [...]
Journal Article
A path forward in the debate over health impacts of endocrine disrupting chemicals
Several recent publications reflect debate on the issue of “endocrine disrupting chemicals” (EDCs), indicating that two seemingly mutually exclusive perspectives are being articulated separately and independently. Considering this, a group of scientists with expertise in basic science, medicine and risk assessment reviewed the various aspects of the debate to identify the most significant areas of dispute and to propose a path forward. We identified four areas of debate. The first is about the definitions for terms such as “endocrine disrupting chemical”, “adverse effects”, and “endocrine system”. The second is focused on elements of hormone action including “potency”, “endpoints”, “timing”, “dose” and “thresholds”. The third addresses the information needed to establish sufficient evidence of harm. Finally, the fourth focuses on the need to develop and the characteristics of transparent, systematic methods to review the EDC literature. Herein we identify areas of general consensus and propose resolutions for these four areas that would allow the field to move beyond the current and, in our opinion, ineffective debate.
Journal Article
Efficient Arsenic Metabolism — The AS3MT Haplotype Is Associated with DNA Methylation and Expression of Multiple Genes Around AS3MT
Arsenic is a very potent toxicant. One major susceptibility factor for arsenic-related toxicity is the efficiency of arsenic metabolism. The efficiency, in turn, is associated with non-coding single nucleotide polymorphisms (SNPs) in the arsenic methyltransferase AS3MT on chromosome 10q24. However, the mechanism of action for these SNPs is not yet clarified. Here, we assessed the influence of genetic variation in AS3MT on DNA methylation and gene expression within 10q24, in people exposed to arsenic in drinking water. DNA was extracted from peripheral blood from women in the Argentinean Andes (N = 103) and from cord blood from new-borns in Bangladesh (N = 127). AS3MT SNPs were analyzed with Sequenom or Taqman assays. Whole genome epigenetic analysis with Infinium HumanMethylation450 BeadChip was performed on bisulphite-treated DNA. Whole genome gene expression analysis was performed with Illumina DirectHyb HumanHT-12 v4.0 on RNA from peripheral blood. Arsenic exposure was assessed by HPLC-ICPMS. In the Argentinean women, the major AS3MT haplotype, associated with more efficient arsenic metabolism, showed increased methylation of AS3MT (p = 10(-6)) and also differential methylation of several other genes within about 800 kilobasepairs: CNNM2 (p<10(-16)), NT5C2 (p<10(-16)), C10orf26 (p = 10(-8)), USMG5 (p = 10(-5)), TRIM8 (p = 10(-4)), and CALHM2 (p = 0.038) (adjusted for multiple comparisons). Similar, but weaker, associations between AS3MT haplotype and DNA methylation in 10q24 were observed in cord blood (Bangladesh). The haplotype-associated altered CpG methylation was correlated with reduced expression of AS3MT and CNNM2 (r(s) = -0.22 to -0.54), and with increased expression of NT5C2 and USMG5 (r(s) = 0.25 to 0.58). Taking other possibly influential variables into account in multivariable linear models did only to a minor extent alter the strength of the associations. In conclusion, the AS3MT haplotype status strongly predicted DNA methylation and gene expression of AS3MT as well as several genes in 10q24. This raises the possibility that several genes in this region are important for arsenic metabolism.
Journal Article
Relative differences in aryl hydrocarbon receptor-mediated response for 18 polybrominated and mixed halogenated dibenzo-P-dioxins and -furans in cell lines from four different species
As a consequence of ubiquitous use of brominated organic chemicals, there is a concern for persistent or increasing environmental levels of polybrominated dibenzo‐p‐dioxins/furans (PBDD/Fs) and mixed polychlorinated and polybrominated di‐benzo‐p‐dioxins/furans (PXDD/Fs). Hence, there is a need to broaden the toxicological and environmental knowledge about these compounds, as a basis for risk assessment. In the study presented here, the relative potencies (REPs) for 18 PBDD/F and PXDD/F congeners were determined in four dioxin‐specific bioassays from different species: dioxin receptor chemically activated luciferase expression assay (DR‐CALUX, rat hepatoma cells), TV101L (human hepatoma cells), and GPC.2D (guinea pig adenoma cells), as well as ethoxyresorufin‐O‐deethylase induction in the fish cell line RTL‐W1 (rainbow trout liver cells). The bioassay specific REP factors presented here enable the assessment of the contribution from PBDD/Fs and PXDD/Fs to total 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) equivalents (TEQs: toxic equivalents), using bioassay analysis. The PBDD/Fs were found to be equally potent as their chlorinated analogues in the three mammalian assays, whereas the PXDD/Fs showed relatively higher potencies. Of special concern were the 2,3,7,8‐substituted penta‐ and tetrahalogenated congeners, for which mean REPs were >1. The 2‐B‐1,3,7,8‐CDD (2‐bromo‐1,3,7,8‐tetrachlorodibenzo‐p‐dioxin) was up to three times more potent than TCDD in individual experiments (on weight basis). The RTL‐W1 was less sensitive to the tested compounds with overall 10‐fold lower REPs than the mammalian cell lines. Although the REP factors exhibited species‐specific differences, overall resembling rank orders of dioxin‐like potency were obtained.
Journal Article
Breaking Patterns of Environmentally Influenced Disease for Health Risk Reduction: Immune Perspectives
Background: Diseases rarely, if ever, occur in isolation. Instead, most represent part of a more complex web or \"pattern\" of conditions that are connected via underlying biological mechanisms and processes, emerge across a lifetime, and have been identified with the aid of large medical databases. Objective: We have described how an understanding of patterns of disease may be used to develop new strategies for reducing the prevalence and risk of major immune-based illnesses and diseases influenced by environmental stimuli. Findings: Examples of recently defined patterns of diseases that begin in childhood include not only metabolic syndrome, with its characteristics of inflammatory dysregulation, but also allergic, autoimmune, recurrent infection, and other inflammatory patterns of disease. The recent identification of major immune-based disease patterns beginning in childhood suggests that the immune system may play an even more important role in determining health status and health care needs across a lifetime than was previously understood. Conclusions: Focusing on patterns of disease, as opposed to individual conditions, offers two important venues for environmental health risk reduction. First, prevention of developmental immunotoxicity and pediatric immune dysfunction can be used to act against multiple diseases. Second, pattern-based treatment of entryway diseases can be tailored with the aim of disrupting the entire disease pattern and reducing the risk of later-life illnesses connected to underlying immune dysfunction. Disease-pattern–based evaluation, prevention, and treatment will require a change from the current approach for both immune safety testing and pediatric disease management.
Journal Article
Risk of Pancreatic Cancer in Female Textile Workers in Shanghai, China, Exposed to Metals, Solvents, Chemicals, and Endotoxin
OBJECTIVE:We studied associations between pancreatic cancer and occupational exposures to metals, solvents, chemicals, and endotoxin in a cohort of female textile workers in Shanghai, China. To assess the longer-term influences of these agents on pancreatic cancer we extended follow-up of this previously studied cohort.
METHODS:We utilized a job exposure matrix to assess occupational exposures for 481 pancreatic cancer cases and a randomly selected sub-cohort of 3191 non-cases. We calculated hazard ratios and 95% confidence intervals using Cox proportional hazards modeling adapted for the case-cohort design.
RESULTS:We observed a statistically significant trend of increasing hazard ratios associated with solvent exposure, but no associations with any of the remaining occupational exposures, including endotoxin and metals.
CONCLUSIONS:Our findings of increasing risk of pancreatic cancer with solvent exposures are consistent with published literature.
Journal Article