AhR transcriptional activity in serum of Inuits across Greenlandic districts

<p>Abstract</p> <p>Background</p> <p>Human exposure to lipophilic persistent organic pollutants (POPs) including polychlorinated dibenzo-<it>p</it>-dioxins/furans (PCDDs/PCDFs), polychlorinated biphenyls (PCBs) and organochlorine pesticide is ubiquitous. The individual is exposed to a complex mixture of POPs being life-long beginning during critical developmental windows. Exposure to POPs elicits a number of species- and tissue-specific toxic responses, many of which involve the aryl hydrocarbon receptor (AhR). The aim of this study was to compare the actual level of integrated AhR transcriptional activity in the lipophilic serum fraction containing the actual POP mixture among Inuits from different districts in Greenland, and to evaluate whether the AhR transactivity is correlated to the bio-accumulated POPs and/or lifestyle factors.</p> <p>Methods</p> <p>The study included 357 serum samples from the Greenlandic districts: Nuuk and Sisimiut (South West Coast), Qaanaaq (North Coast) and Tasiilaq (East Coast). The bio-accumulated serum POPs were extracted by ethanol: hexane and clean-up on Florisil columns. Effects of the serum extract on the AhR transactivity was determined using the Hepa 1.12cR mouse hepatoma cell line carrying an AhR-luciferase reporter gene, and the data was evaluated for possible association to the serum levels of 14 PCB congeners, 10 organochlorine pesticide residues and/or lifestyle factors.</p> <p>Results</p> <p>In total 85% of the Inuit samples elicited agonistic AhR transactivity in a district dependent pattern. The median level of the AhR-TCDD equivalent (AhR-TEQ) of the separate genders was similar in the different districts. For the combined data the order of the median AhR-TEQ was Tasiilaq > Nuuk ≥ Sisimiut > Qaanaaq possibly being related to the different composition of POPs. In overall, the AhR transactivity was inversely correlated to the levels of sum POPs, age and/or intake of marine food.</p> <p>Conclusion</p> <p>i) We observed that the proportion of dioxin like (DL) compounds in the POP mixture was the dominating factor affecting the level of serum AhR transcriptional activity even at very high level of non DL-PCBs; ii) The inverse association between the integrated serum AhR transactivity and sum of POPs might be explained by the higher level of compounds antagonizing the AhR function probably due to selective POP bioaccumulation in the food chain.</p

Xenohormone transactivities are inversely associated to serum POPs in Inuit

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Occupy: 'struggles for the common or an 'anti-politics of dignity? Reflections on Hardt and Negri and John Holloway

This article provides a critical examination of Michael Hardt and Antonio Negri’s and John Holloway’s theory of revolutionary subjectivity, and does so by applying their theories to the Occupy movement of 2011. Its central argument is that one should avoid collapsing ‘autonomist’ and ‘open’ Marxism, for whilst both approaches share Tronti’s (1979) insistence on the constituent role of class struggle, and also share an emphasis on a prefigurative politics which engages a non-hierarchical and highly participatory politics, there nevertheless remain some significant differences between their approaches. Ultimately, when applied to Occupy Movement whilst their theory isn’t entirely unproblematic, I will argue that Hardt and Negri’s ‘autonomist’ approach offers the stronger interpretation, due mainly to their revised historical materialism

(Im)possibilities of Autonomy:? Social Movements In and Beyond Capital, the State and Development

In this paper we interrogate the demand and practice of autonomy in social movements. We begin by identifying three main conceptions of autonomy: (1) autonomous practices vis-à-vis capital; (2) self-determination and independence from the state; and (3) alternatives to hegemonic discourses of development. We then point to limits associated with autonomy and discuss how demands for autonomy are tied up with contemporary re-organizations of: (1) the capitalist workplace, characterized by discourses of autonomy, creativity and self-management; (2) the state, which increasingly outsources public services to independent, autonomous providers, which often have a more radical, social movement history; and (3) regimes of development, which today often emphasize local practices, participation and self-determination. This capturing of autonomy reminds us that autonomy can never be fixed. Instead, social movements' demands for autonomy are embedded in specific social, economic, political and cultural contexts, giving rise to possibilities as well as impossibilities of autonomous practices

European economic constitution and the transformation of democracy : on class and the state of law

In the context of contemporary analyses of the Europe Union as a post-democratic form of economic governance, this article explores the (ordo)liberal character of monetary union as a regime of imposed liberty. The argument holds that rather than forcing the member states into retreat, the economic constitution of Europe strengthens their liberal foundation, securing their utility as the organised force of a mode of social reproduction founded on free labour. It develops the character of the liberal state as the political form of a free market economy with reference to Adam Smith’s classical political economy and the German ordoliberal tradition, which calls for a rule-based system of federated forms of economic governance to secure a free labour economy in conditions of mass democratic aspirations for a freedom from want. It explores the rationale of the ordoliberal distinction between the liberal character and the democratic character of the state and, in this context, assesses the meaning of liberal democracy in a post-democratic Eurozone

Inter-population variations in concentrations, determinants of and correlations between 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE): a cross-sectional study of 3161 men and women from Inuit and European populations.

The study is part of a collaborative project (Inuendo), aiming to assess the impact of dietary persistent organochlorine pollutants (POPs) on human fertility. The aims with the present study are to analyze inter-population variations in serum concentrations of 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis (p-chlorophenyl)-ethylene (p,p'-DDE), to assess inter-population variations in biomarker correlations, and to evaluate the relative impact of different determinants for the inter-individual variations in POP-biomarkers. CB-153 concentrations were much higher in Inuits and Swedish fishermen's populations than in the populations from Eastern Europe, whereas the pattern was different for p,p'-DDE showing highest concentrations in the Kharkiv population. The correlations between the POP-biomarkers varied considerably between the populations, underlining that exposure sources differ and that the choice of representative biomarkers of overall POP exposure has to be based on an analysis of the specific exposure situation for each population. Age and gender were consistent determinants of serum POPs; seafood was of importance only in the Inuit and Swedish populations

Inhibition of E2-induced expression of BRCA1 by persistent organochlorines

BACKGROUND: Environmental persistent organochlorines (POCs) biomagnify in the food chain, and the chemicals are suspected of being involved in a broad range of human malignancies. It is speculated that some POCs that can interfere with estrogen receptor-mediated responses are involved in the initiation and progression of human breast cancer. The tumor suppressor gene BRCA1 plays a role in cell-cycle control, in DNA repair, and in genomic stability, and it is often downregulated in sporadic mammary cancers. The aim of the present study was to elucidate whether POCs have the potential to alter the expression of BRCA1. METHODS: Using human breast cancer cell lines MCF-7 and MDA-MB-231, the effect on BRCA1 expression of chemicals belonging to different classes of organochlorine chemicals (the pesticide toxaphene, 2,3,7,8-tetrachlorodibenzo-p-dioxin, and three polychlorinated biphenyls [PCB#138, PCB#153 and PCB#180]) was measured by a reporter gene construct carrying 267 bp of the BRCA1 promoter. A twofold concentration range was analyzed in MCF-7, and the results were supported by northern blot analysis of BRCA1 mRNA using the highest concentrations of the chemicals. RESULTS: All three polychlorinated biphenyls and 2,3,7,8-tetrachlorodibenzo-p-dioxin reduced 17β-estradiol (E2)-induced expression as well as basal reporter gene expression in both cell lines, whereas northern blot analysis only revealed a downregulation of E2-induced BRCA1 mRNA expression in MCF-7 cells. Toxaphene, like E2, induced BRCA1 expression in MCF-7. CONCLUSION: The present study shows that some POCs have the capability to alter the expression of the tumor suppressor gene BRCA1 without affecting the cell-cycle control protein p21(Waf/Cip1). Some POCs therefore have the potential to affect breast cancer risk