Dioxin-like activities in serum across European and Inuit populations

BackgroundPersistent organic pollutants (POPs) such as polychlorinated dibenzo-p-dioxins/furans, polychlorinated biphenyls (PCBs) and organochlorine pesticides can cause a series of adverse effects on e.g. reproduction in animals and humans, many of which involve the aryl hydrocarbon receptor (AhR). The aim of the present study was to compare the integrated serum level of AhR mediated activity among European and Inuit populations, and evaluate whether the activity was associated to the selected POP markers, 2,2',4,4',5,5'-hexachlorobiphenyl (CB-153) and 1,1-dichloro-2,2-bis(p-chlorophenyl)-ethylene (p,p'-DDE).MethodsThe study included 338 males from Greenland (Inuit's), Sweden, Warsaw (Poland) and Kharkiv (Ukraine). The AhR transactivity of serum extracts alone (AhRag) and competitive AhR activity (AhRcomp) upon co-exposure with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were determined in the lipophilic serum fraction containing the POPs using the AhR mediated luciferase reporter Hepa1.12cR cell assay.ResultsThe European groups showed higher median level of AhR-TEQ (TCDD toxic equivalents) compared to the Inuit's, whereas higher incidence of Inuits sample further induced AhRcomp activity. Neither AhRag nor AhR-TEQ were correlated to CB-153 or p,p'-DDE for any of the study groups. Multiple regressions showed a significant heterogeneity of association between the CB-153 and the AhRcomp across the study groups, and accordingly a negative association between AhRcomp and CB-153 was found for the Kharkiv group.ConclusionNo consistent correlation between AhR activities and two POP markers was found. Although the difference of AhRag between European and Inuit men could not be explained by CB-153 or p,p'-DDE levels alone, we believe that the variation of AhR serum activity reflects different pattern of POP exposure, genetics and/or life style factors.

[1]  R. Tukey,et al.  Using the metabolism of PAHs in a human cell line to characterize environmental samples. , 2000, Environmental toxicology and pharmacology.

[2]  E. Bonefeld‐Jørgensen,et al.  Effect of pesticides on estrogen receptor transactivation in vitro: A comparison of stable transfected MVLN and transient transfected MCF-7 cells , 2005, Molecular and Cellular Endocrinology.

[3]  S. Safe,et al.  Cellular and molecular biology of aryl hydrocarbon (Ah) receptor-mediated gene expression. , 1995, Archives of toxicology. Supplement. = Archiv fur Toxikologie. Supplement.

[4]  S. Gingras,et al.  Exposure of remote maritime populations to coplanar PCBs. , 1994, Environmental health perspectives.

[5]  A. Grochowalski.  PCDDs and PCDFs concentration in combustion gases and bottom ash from incineration of hospital wastes in Poland. , 1998, Chemosphere.

[6]  M. Longnecker,et al.  Correlations among Human Plasma Levels of Dioxin-Like Compounds and Polychlorinated Biphenyls (PCBs) and Implications for Epidemiologic Studies , 2000, Archives of environmental health.

[7]  A. Vinggaard,et al.  Effects of currently used pesticides in the AhR-CALUX assay: comparison between the human TV101L and the rat H4IIE cell line. , 2003, Toxicology.

[8]  N Debacker,et al.  Validation of the CALUX bioassay for PCDD/F analyses in human blood plasma and comparison with GC-HRMS. , 2004, Talanta.

[9]  P. Schepens,et al.  Comparison of chemical-activated luciferase gene expression bioassay and gas chromatography for PCB determination in human serum and follicular fluid. , 2000, Environmental health perspectives.

[10]  D. Smith,et al.  Worldwide trends in DDT levels in human breast milk. , 1999, International journal of epidemiology.

[11]  L. Hagmar,et al.  Mortality and cancer incidence among women with a high consumption of fatty fish contaminated with persistent organochlorine compounds. , 1995, Scandinavian journal of work, environment & health.

[12]  J. Jacobson,et al.  Prenatal exposure of the northern Québec Inuit infants to environmental contaminants. , 2001, Environmental health perspectives.

[13]  K. Hooper,et al.  Workshop on perinatal exposure to dioxin-like compounds. I. Summary. , 1995 .

[14]  S. Safe,et al.  Polychlorinated biphenyls (PCBs): environmental impact, biochemical and toxic responses, and implications for risk assessment. , 1994, Critical reviews in toxicology.

[15]  Safe,et al.  Toxic equivalency factors (TEFs) for PCBs, PCDDs, PCDFs for humans and wildlife. , 1998, Environmental health perspectives.

[16]  M. Denison,et al.  Comparison of recombinant cell bioassays for the detection of Ah receptor agonists , 2004, BioFactors.

[17]  L S Birnbaum,et al.  Functional aspects of developmental toxicity of polyhalogenated aromatic hydrocarbons in experimental animals and human infants. , 1995, European journal of pharmacology.

[18]  J. Giesy,et al.  Species-specific recombinant cell lines as bioassay systems for the detection of 2,3,7,8-tetrachlorodibenzo-p-dioxin-like chemicals. , 1996, Fundamental and applied toxicology : official journal of the Society of Toxicology.

[19]  M. Denison,et al.  Development and modification of a recombinant cell bioassay to directly detect halogenated and polycyclic aromatic hydrocarbons in serum. , 2000, Toxicological sciences : an official journal of the Society of Toxicology.

[20]  G. Clark,et al.  Dioxin-Like TEQ of women from the Seveso, Italy area by ID-HRGC/HRMS and CALUX , 2005, Journal of Exposure Analysis and Environmental Epidemiology.

[21]  A M Vinggaard,et al.  Effect of highly bioaccumulated polychlorinated biphenyl congeners on estrogen and androgen receptor activity. , 2001, Toxicology.

[22]  M. Schalk,et al.  Species-specific antagonism of Ah receptor action by 2,2',5,5'-tetrachloro- and 2,2',3,3'4,4'-hexachlorobiphenyl. , 1995, European journal of pharmacology.

[23]  K. Hooper,et al.  Workshop on perinatal exposure to dioxin-like compounds. I. Summary. , 1995, Environmental health perspectives.

[24]  S. Safe,et al.  Polychlorinated biphenyls (PCBs), dibenzo-p-dioxins (PCDDs), dibenzofurans (PCDFs), and related compounds: environmental and mechanistic considerations which support the development of toxic equivalency factors (TEFs). , 1990, Critical reviews in toxicology.

[25]  M. Machala,et al.  Aryl hydrocarbon receptor‐mediated and estrogenic activities of oxygenated polycyclic aromatic hydrocarbons and azaarenes originally identified in extracts of river sediments , 2001, Environmental toxicology and chemistry.

[26]  J. Goldstein,et al.  Interaction of hexachlorobenzene with the receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin in vitro and in vivo. Evidence that hexachlorobenzene is a weak Ah receptor agonist. , 1989, Archives of biochemistry and biophysics.

[27]  J. Weber,et al.  Circumpolar maternal blood contaminant survey, 1994-1997 organochlorine compounds. , 2004, The Science of the total environment.

[28]  N. Bunce,et al.  Interaction between halogenated aromatic compounds in the Ah receptor signal transduction pathway , 2004, Environmental toxicology.

[29]  L. Hagmar,et al.  Fertility in four regions spanning large contrasts in serum levels of widespread persistent organochlorines: a cross-sectional study , 2005, Environmental health : a global access science source.

[30]  G. Clark,et al.  Trace contamination with dioxin-like chemicals: evaluation of bioassay-based TEQ determination for hazard assessment and regulatory responses , 2001 .

[31]  Kyle Steenland,et al.  Dioxin Revisited: Developments Since the 1997 IARC Classification of Dioxin as a Human Carcinogen , 2004, Environmental health perspectives.

[32]  M. Feeley,et al.  Biomarker Measurements in a Coastal Fish-Eating Population Environmentally Exposed to Organochlorines , 2005, Environmental health perspectives.

[33]  L. Hagmar,et al.  Reproductive Hormone Levels in Men Exposed to Persistent Organohalogen Pollutants: A Study of Inuit and Three European Cohorts , 2006, Environmental health perspectives.

[34]  H. Autrup,et al.  Effect of toxaphene on estrogen receptor functions in human breast cancer cells. , 1997, Carcinogenesis.

[35]  T. Klonisch,et al.  Molecular interactions of the aryl hydrocarbon receptor and its biological and toxicological relevance for reproduction. , 2005, Reproduction.

[36]  P. de Knijff,et al.  DNA-Polymorphisms and Plasma Levels of Vascular Disease Risk Factors in Greenland Inuit , 1999, Thrombosis and Haemostasis.

[37]  M. van den Berg,et al.  Impact of Polychlorinated Biphenyls Contamination on Estrogenic Activity in Human Male Serum , 2005, Environmental health perspectives.

[38]  L. Hagmar,et al.  Fish consumption and exposure to persistent organochlorine compounds, mercury, selenium and methylamines among Swedish fishermen. , 1995, Scandinavian journal of work, environment & health.

[39]  J. Gustafsson,et al.  Aryl hydrocarbon receptor-mediated signal transduction. , 1997, Critical reviews in toxicology.

[40]  Gianluca Gallerano.  Quality of Life and Management of Living Resources , 2004 .

[41]  J. J. Amaral Mendes.  The endocrine disrupters: a major medical challenge. , 2002, Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association.

[42]  V. Nelen,et al.  Persistent organochlorine pollutants in human serum of 50-65 years old women in the Flanders Environmental and Health Study (FLEHS). Part 1: Concentrations and regional differences. , 2002, Chemosphere.

[43]  E. De Pauw,et al.  Importance of clean-up for comparison of TEQ-values obtained by CALUX and chemo-analysis. , 2004, Talanta.

[44]  Richard E. Peterson,et al.  Human risk assessment and TEFs , 2000, Food additives and contaminants.

[45]  L. Hagmar,et al.  Exposure to PCBs and p,p′-DDE and Human Sperm Chromatin Integrity , 2004, Environmental health perspectives.

[46]  N. Kaminski,et al.  Antagonism of aryl hydrocarbon receptor-dependent induction of CYP1A1 and inhibition of IgM expression by di-ortho-substituted polychlorinated biphenyls. , 2003, Toxicology and applied pharmacology.

[47]  Lorenzo Tomatis,et al.  Dichlorodiphenyltrichloroethane (DDT): ubiquity, persistence, and risks. , 2002, Environmental health perspectives.

[48]  V. Nelen,et al.  Persistent organochlorine pollutants in human serum of 50-65 years old women in the Flanders Environmental and Health Study (FLEHS). Part 2: Correlations among PCBs, PCDD/PCDFs and the use of predictive markers. , 2002, Chemosphere.

[49]  J. Ludwicki,et al.  Organochlorine Pesticides, HCB, and PCBs in Human Milk in Poland , 1997, Bulletin of environmental contamination and toxicology.

[50]  L. Hagmar,et al.  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 , 2005, Environmental health : a global access science source.

[51]  E. De Pauw,et al.  Levels and profiles of PCDDs, PCDFs and cPCBs in Belgian breast milk. Estimation of infant intake. , 2002, Chemosphere.

[52]  I. Hertz-Picciotto,et al.  Determinants of serum polychlorinated biphenyls and organochlorine pesticides measured in women from the child health and development study cohort, 1963-1967. , 2002, Environmental health perspectives.

[53]  B. Gladen,et al.  Organochlorines in breast milk from two cities in Ukraine. , 1999, Environmental health perspectives.

[54]  L. Hagmar,et al.  Influence of the consumption of fatty Baltic Sea fish on plasma levels of halogenated environmental contaminants in Latvian and Swedish men. , 2000, Environmental health perspectives.

[55]  J. Weber,et al.  Organochlorine levels in maternal and umbilical cord blood plasma in Arctic Canada. , 2003, The Science of the total environment.

[56]  L. Birnbaum,et al.  Chemically activated luciferase gene expression (CALUX) cell bioassay analysis for the estimation of dioxin-like activity: critical parameters of the CALUX procedure that impact assay results. , 2005, Environmental science & technology.