Xenoestrogenic activity in blood of European and Inuit populations

BackgroundHuman exposure to persistent organic pollutants (POPs) is ubiquitous and found in all individuals. Studies have documented endocrine disrupting effects and impact on reproduction. The aim of the present study was to compare the level of xenoestrogenic activity in serum of groups with varying POP exposure, and to evaluate correlations to the POP biomarkers, 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 358 men: Greenlandic Inuit's, Swedish fishermen, and Warsaw (Poland) and Kharkiv (Ukraine) inhabitants. Xenoestrogenicity of serum extracts alone (XER) and XER competitive (XERcomp) effect on 17β-estradiol induced estrogen receptor (ER) transactivity were assessed in the hormone free, lipophilic serum fraction containing the POPs using the MVLN human breast cancer cell line.ResultsNo agonistic XER activity was exhibited for Inuit serum samples, while 12 – 24% of the European samples had detectable agonistic XER activity. On the contrary, 71% of Inuit serum samples antagonized XERcomp compared to 7 – 30 % in the other regions. XER and XERcomp were not or weakly correlated to the two POP markers. XER activity of Inuit samples was negatively associated to levels of CB-153 and p,p'-DDE. For the Warsaw group a positive and negative correlation between XER and p,p'-DDE and estradiol equivalence level and CB-153 levels was found.ConclusionNo strong consistent association between xenoestrogenic net activity and the two POP markers was found. The results showed that the selected POP markers alone can not predict the integrated xenoestrogenic serum activity. Correlations to the POP markers were found at the extreme edge; the Inuit's and Warsaw study groups eliciting high frequency of samples with ER antagonistic and agonistic activity, respectively. We suggest that the variation in xenoestrogenic serum activity reflects differences in POP exposure mixture, genetic factors and/or life style factors.

[1]  L. Hagmar,et al.  Monitoring of Polychlorinated Biphenyls in Human Blood Plasma: Methodological Developments and Influence of Age, Lactation, and Fish Consumption , 1997, Archives of environmental contamination and toxicology.

[2]  L. Hagmar,et al.  Epidemiological evidence on reproductive effects of persistent organochlorines in humans. , 2004, Reproductive toxicology.

[3]  E. Bonefeld‐Jørgensen,et al.  SPE-HPLC purification of endocrine-disrupting compounds from human serum for assessment of xenoestrogenic activity , 2006, Analytical and bioanalytical chemistry.

[4]  S. Safe,et al.  Hydroxylated polychlorinated biphenyls (PCBs) as estrogens and antiestrogens: structure-activity relationships. , 1997, Toxicology and applied pharmacology.

[5]  A. Kortenkamp,et al.  Mixtures of four organochlorines enhance human breast cancer cell proliferation. , 2001, Environmental health perspectives.

[6]  Anne Marie Vinggaard,et al.  Effects of currently used pesticides in assays for estrogenicity, androgenicity, and aromatase activity in vitro. , 2002, Toxicology and applied pharmacology.

[7]  D. Carpenter,et al.  Human health and chemical mixtures: an overview. , 1998, Environmental Health Perspectives.

[8]  K. Korach,et al.  Molecular mechanism of estrogen action in the male: insights from the estrogen receptor null mice. , 2001, Reproduction, fertility, and development.

[9]  J W Bridges,et al.  Integrated risk assessment and endocrine disrupters. , 2004, Toxicology.

[10]  M. Juchau,et al.  Biotransformation of all-trans-retinal, 13-cis-retinal, and 9-cis-retinal catalyzed by conceptal cytosol and microsomes. , 1997, Biochemical pharmacology.

[11]  R. Hess Estrogen in the adult male reproductive tract: A review , 2003, Reproductive biology and endocrinology : RB&E.

[12]  A. Sasco,et al.  Breast Cancer Risk and the Combined Effect of Environmental Estrogens , 2004, Cancer Causes & Control.

[13]  D Gagne,et al.  A new cellular model of response to estrogens: a bioluminescent test to characterize (anti) estrogen molecules. , 1990, BioTechniques.

[14]  E. Bonefeld‐Jørgensen,et al.  Effect of in vitro estrogenic pesticides on human oestrogen receptor alpha and beta mRNA levels. , 2004, Toxicology letters.

[15]  J. Arunakaran,et al.  Effect of polychlorinated biphenyl, Aroclor 1254 on rat epididymis. , 2003, The Indian journal of medical research.

[16]  E. Bonefeld‐Jørgensen,et al.  Effect of in vitro estrogenic pesticides on human oestrogen receptor α and β mRNA levels , 2004 .

[17]  Ana Rivas,et al.  Assessment of total effective xenoestrogen burden in adipose tissue and identification of chemicals responsible for the combined estrogenic effect , 2004, Analytical and bioanalytical chemistry.

[18]  E. Bonefeld‐Jørgensen The Human Health Effect Programme in Greenland, a review. , 2004, The Science of the total environment.

[19]  D. Sager,et al.  Effect of early postnatal exposure to polychlorinated biphenyls (PCBs) on fertility in male rats , 1987, Bulletin of environmental contamination and toxicology.

[20]  Frank Claessens,et al.  Selective DNA recognition by the androgen receptor as a mechanism for hormone-specific regulation of gene expression. , 2003, Molecular genetics and metabolism.

[21]  H. Leffers,et al.  Comparison of Short-Term Estrogenicity Tests for Identification of Hormone-Disrupting Chemicals , 1999, Environmental health perspectives.

[22]  Maria Sjöberg,et al.  Mechanisms of estrogen receptor signaling: convergence of genomic and nongenomic actions on target genes. , 2005, Molecular endocrinology.

[23]  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.

[24]  D. Vorojeikina,et al.  Transcriptional activation of the human estrogen receptor by DDT isomers and metabolites in yeast and MCF-7 cells. , 1997, Biochemical pharmacology.

[25]  P. Ayotte,et al.  Breast cancer and organochlorines , 1994, The Lancet.

[26]  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.

[27]  L. Hagmar,et al.  Exposure to CB-153 and p,p'-DDE and male reproductive function. , 2004, Human reproduction.

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

[29]  B. Deutch,et al.  Smoking as a Determinant of High Organochlorine Levels in Greenland , 2003, Archives of environmental health.

[30]  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.

[31]  L. Gray,et al.  Persistent DDT metabolite p,p'–DDE is a potent androgen receptor antagonist , 1995, Nature.

[32]  N. Olea,et al.  Development of a marker of estrogenic exposure in human serum. , 1995, Clinical chemistry.

[33]  T. Zacharewski,et al.  Interactions between human plasma sex hormone-binding globulin and xenobiotic ligands , 2000, The Journal of Steroid Biochemistry and Molecular Biology.

[34]  G L Kimmel,et al.  Developmental and reproductive toxicity of dioxins and related compounds: cross-species comparisons. , 1993, Critical reviews in toxicology.

[35]  Mariana F. Fernández,et al.  Human exposure to endocrine disrupters: Standardisation of a marker of estrogenic exposure in adipose tissue , 2001, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[36]  S. Teichmann,et al.  Nuclear Receptors: The Evolution of Diversity , 2004, Science's STKE.

[37]  S. Carreau Estrogens--male hormones? , 2003, Folia histochemica et cytobiologica.

[38]  E. Bonefeld‐Jørgensen,et al.  Effects of the pesticides prochloraz and methiocarb on human estrogen receptor α and β mRNA levels analyzed by on-line RT-PCR , 2004 .

[39]  M. Longnecker,et al.  Characterization of potential endocrine-related health effects at low-dose levels of exposure to PCBs. , 1999, Environmental health perspectives.

[40]  H. Adami,et al.  Serum concentrations of organochlorines in men: a search for markers of exposure. , 2000, The Science of the total environment.

[41]  G. Steinhardt Endocrine disruption and hypospadias. , 2004, Advances in experimental medicine and biology.

[42]  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.

[43]  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.

[44]  M. Fielden,et al.  Effects of gestational and lactational exposure to Aroclor 1242 on sperm quality and in vitro fertility in early adult and middle-aged mice. , 2001, Reproductive toxicology.

[45]  A. Kortenkamp,et al.  Combining xenoestrogens at levels below individual no-observed-effect concentrations dramatically enhances steroid hormone action. , 2002, Environmental health perspectives.

[46]  E. Gregoraszczuk,et al.  Congener-specific accumulation of polychlorinated biphenyls in ovarian follicular wall follows repeated exposure to PCB 126 and PCB 153. Comparison of tissue levels of PCB and biological changes. , 2003, Chemosphere.

[47]  A. Schecter,et al.  Polychlorinated dibenzo-p-dioxins, polychlorinated dibenzofurans, and coplanar polychlorinated biphenyls in breast milk from two cities in Ukraine. , 1999, Journal of toxicology and environmental health. Part A.

[48]  H. Ostrer,et al.  Immunolocalization of androgen receptor and estrogen receptors alpha and beta in human fetal testis and epididymis. , 2005, The Journal of urology.

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

[50]  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.

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

[52]  Jesper Bo Nielsen,et al.  Assessment of xenoestrogenic exposure by a biomarker approach: application of the E-Screen bioassay to determine estrogenic response of serum extracts , 2003, Environmental health : a global access science source.

[53]  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.

[54]  E. Bonefeld‐Jørgensen,et al.  Effects of the pesticides prochloraz and methiocarb on human estrogen receptor alpha and beta mRNA levels analyzed by on-line RT-PCR. , 2004, Toxicology in vitro : an international journal published in association with BIBRA.

[55]  H. Ostrer,et al.  IMMUNOLOCALIZATION OF ANDROGEN RECEPTOR AND ESTROGEN RECEPTORS α AND β IN HUMAN FETAL TESTIS AND EPIDIDYMIS , 2005 .