Xenohormone transactivities are inversely associated to serum POPs in Inuit

AbstractBackgroundThe persistent organic pollutants (POPs) are highly lipophilic and resistant to biodegradation and found in e.g. seafood and marine mammals. Greenlandic Inuit have high intake of marine food and thus high POP burden that varies according to local conditions and dietary preference. We do for the very first time report the serum POP related non-steroidal xenohormone activity of Inuit across Greenland. The aims were 1) to determine the integrated xenohormone bioactivities as an exposure biomarker of the actual lipophilic serum POP mixture measuring the effect on estrogen (ER) and androgen receptor (AR) transactivity in citizens from different Greenlandic districts and 2) to evaluate associations to serum POP markers (14 PCBs and 10 pesticides) and lifestyle characteristics.MethodsSerum samples from 121 men and 119 women from Nuuk, Sisimiut and Qaanaaq were extracted using SPE-HPLC fractionation to obtain the serum POP fraction free of endogenous hormones. The serum POP fraction was used for determination of xenohormone transactivity using ER and AR reporter gene assays.ResultsIn overall, the xenohormone transactivities differed between districts as well as between the genders. Associations between the transactivities and age, n-3/n-6 and smoker years were observed. The xenoestrogenic and xenoandrogenic transactivities correlated negatively to the POPs for the combined female and male data, respectively.ConclusionThe non-steroidal xenohormone transactivities can be used as an integrated biomarker of POP exposure and lifestyle characteristics. The actual serum POP mixtures antagonized the age adjusted sex hormone receptor functions. Comparison of different study populations requires in addition to age inclusion of diet and lifestyle factors.

[1]  H. Akaza,et al.  Effects of single non-ortho, mono-ortho, and di-ortho chlorinated biphenyls on cell functions and proliferation of the human prostatic carcinoma cell line, LNCaP. , 2003, Reproductive toxicology.

[2]  K. Hayakawa,et al.  A role of aryl hydrocarbon receptor in the antiandrogenic effects of polycyclic aromatic hydrocarbons in LNCaP human prostate carcinoma cells , 2003, Archives of Toxicology.

[3]  M. Glasius,et al.  Persistent halogenated compounds in black guillemots (Cepphus grylle) from Greenland--levels, compound patterns and spatial trends. , 2004, Marine pollution bulletin.

[4]  H. Pedersen,et al.  Dietary composition in Greenland 2000, plasma fatty acids and persistent organic pollutants. , 2004, The Science of the total environment.

[5]  S. Safe,et al.  Ah receptor agonists as endocrine disruptors: antiestrogenic activity and mechanisms. , 1998, Toxicology letters.

[6]  C. Tohyama,et al.  Cross-talk between 2,3,7,8-tetrachlorodibenzo-p-dioxin and testosterone signal transduction pathways in LNCaP prostate cancer cells. , 1999, Biochemical and biophysical research communications.

[7]  L. Barrie,et al.  Arctic contaminants: sources, occurrence and pathways. , 1992, The Science of the total environment.

[8]  J. Bonde,et al.  Relation between serum xenobiotic-induced receptor activities and sperm DNA damage and sperm apoptotic markers in European and Inuit populations. , 2007, Reproduction.

[9]  P G Mulder,et al.  Effects of environmental exposure to polychlorinated biphenyls and dioxins on cognitive abilities in Dutch children at 42 months of age. , 1999, The Journal of pediatrics.

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

[11]  G. Asmund,et al.  Contaminants, diet, plasma fatty acids and smoking in Greenland 1999-2005. , 2007, The Science of the total environment.

[12]  É. Dewailly,et al.  Very high concentrations of n-3 fatty acids in peri-and postmenopausal Inuit women from Greenland , 2004, International journal of circumpolar health.

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

[14]  Jorma Toppari,et al.  Human Breast Milk Contamination with Phthalates and Alterations of Endogenous Reproductive Hormones in Infants Three Months of Age , 2005, Environmental health perspectives.

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

[16]  T. Schrader,et al.  Effects of Aroclors and individual PCB congeners on activation of the human androgen receptor in vitro. , 2003, Reproductive toxicology.

[17]  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.

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

[19]  A. Tjønneland,et al.  Adipose tissue fatty acids as biomarkers of dietary exposure in Danish men and women. , 1993, The American journal of clinical nutrition.

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

[21]  J. Weber,et al.  Concentration of organochlorines in human brain, liver, and adipose tissue autopsy samples from Greenland. , 1999, Environmental health perspectives.

[22]  G. Ankley,et al.  Masculinization of female mosquitofish in Kraft mill effluent-contaminated Fenholloway River water is associated with androgen receptor agonist activity. , 2001, Toxicological sciences : an official journal of the Society of Toxicology.

[23]  P. Grandjean,et al.  Xeno-oestrogenic activity in serum as marker of occupational pesticide exposure , 2007, Occupational and Environmental Medicine.

[24]  Tanja Krüger,et al.  Xenoandrogenic Activity in Serum Differs across European and Inuit Populations , 2007, Environmental health perspectives.

[25]  J. McLachlan,et al.  Altered Breast Development in Young Girls from an Agricultural Environment , 2006, Environmental health perspectives.

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

[27]  R. Kruse,et al.  Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure , 2005, Environmental health perspectives.

[28]  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.

[29]  M. Dalgaard,et al.  The combined antiandrogenic effects of five commonly used pesticides. , 2004, Toxicology and applied pharmacology.

[30]  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.

[31]  Tanja Krüger,et al.  Xenobiotic activity in serum and sperm chromatin integrity in European and inuit populations , 2008, Molecular reproduction and development.

[32]  G. Asmund,et al.  Dietary composition and contaminants in north Greenland, in the 1970s and 2004. , 2006, The Science of the total environment.

[33]  L. Gray,et al.  Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. , 2002, Environmental health perspectives.

[34]  B. Deutch,et al.  High human plasma levels of organochlorine compounds in Greenland. Regional differences and lifestyle effects. , 2000, Danish medical bulletin.

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

[36]  L. Gray,et al.  Environmental hormone disruptors: evidence that vinclozolin developmental toxicity is mediated by antiandrogenic metabolites. , 1994, Toxicology and applied pharmacology.

[37]  R. Dietz,et al.  Levels and spatial and temporal trends of contaminants in Greenland biota: an updated review. , 2004, The Science of the total environment.

[38]  Y. F. Li,et al.  Contaminants in the Canadian Arctic: 5 years of progress in understanding sources, occurrence and pathways. , 2000, The Science of the total environment.

[39]  S. Safe,et al.  Inhibitory aryl hydrocarbon receptor-estrogen receptor alpha cross-talk and mechanisms of action. , 2003, Chemical research in toxicology.

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

[41]  M. Dalgaard,et al.  Antiandrogenic effects in vitro and in vivo of the fungicide prochloraz. , 2002, Toxicological sciences : an official journal of the Society of Toxicology.

[42]  A M Vinggaard,et al.  Environmental polycyclic aromatic hydrocarbons affect androgen receptor activation in vitro. , 2000, Toxicology.

[43]  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.

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

[45]  Mogens Erlandsen,et al.  Xenoestrogenic activity in blood of European and Inuit populations , 2006, Environmental health : a global access science source.

[46]  I. Huhtaniemi,et al.  Screening of some anti-androgenic endocrine disruptors using a recombinant cell-based in vitro bioassay , 2004, The Journal of Steroid Biochemistry and Molecular Biology.

[47]  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.

[48]  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.

[49]  P. Ayotte,et al.  Inuit exposure to organochlorines through the aquatic food chain in arctic québec. , 1993, Environmental health perspectives.

[50]  Jens Peter Bonde,et al.  Dioxin-like activities in serum across European and Inuit populations , 2006, Environmental health : a global access science source.

[51]  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.

[52]  Martin Scholze,et al.  Dysgenesis and histological changes of genitals and perturbations of gene expression in male rats after in utero exposure to antiandrogen mixtures. , 2007, Toxicological sciences : an official journal of the Society of Toxicology.

[53]  J. Toppari,et al.  Environmental effects on hormonal regulation of testicular descent , 2006, The Journal of Steroid Biochemistry and Molecular Biology.

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

[55]  J. McLachlan,et al.  From malformations to molecular mechanisms in the male: three decades of research on endocrine disrupters , 2001, APMIS : acta pathologica, microbiologica, et immunologica Scandinavica.

[56]  S. Ahmed,et al.  The immune system as a potential target for environmental estrogens (endocrine disrupters): a new emerging field. , 2000, Toxicology.

[57]  M. Long,et al.  AhR transcriptional activity in serum of Inuits across Greenlandic districts , 2007, Environmental health : a global access science source.