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Hf Berntsen - One of the best experts on this subject based on the ideXlab platform.

  • Human blood-based exposure levels of Persistent Organic Pollutant (POP) mixtures antagonise androgen receptor transactivation and translocation
    'Elsevier BV', 2019
    Co-Authors: Mccomb J, Ig Mills, Muller M, Hf Berntsen, Ke Zimmer, Ropstad E, Verhaegen S, Connolly L
    Abstract:

    INTRODUCTION:Human exposure to Persistent Organic Pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. AIM:To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. MATERIALS AND METHODS:The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. RESULTS:No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P 

  • human blood based exposure levels of Persistent Organic Pollutant pop mixtures antagonise androgen receptor transactivation and translocation
    Environment International, 2019
    Co-Authors: Jonathan Mccomb, Hf Berntsen, Ian G Mills, Marc Muller, Karin Elisabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly
    Abstract:

    Abstract Introduction Human exposure to Persistent Organic Pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. Aim To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. Materials and methods The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. Results No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P  Conclusion Taken together, some combinations of POP mixtures can interfere with AR translocation. However, in the transactivation assay, these combinations did not affect gene transactivation. Other POP combinations were identified here as modulators of AR-induced gene transactivation without affecting AR translocation. Thus, to fully evaluate the effect of environmental toxins on AR signalling, both types of assays need to be applied.

Lisa Connolly - One of the best experts on this subject based on the ideXlab platform.

  • human blood based exposure levels of Persistent Organic Pollutant pop mixtures antagonise androgen receptor transactivation and translocation
    Environment International, 2019
    Co-Authors: Jonathan Mccomb, Hf Berntsen, Ian G Mills, Marc Muller, Karin Elisabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly
    Abstract:

    Abstract Introduction Human exposure to Persistent Organic Pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. Aim To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. Materials and methods The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. Results No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P  Conclusion Taken together, some combinations of POP mixtures can interfere with AR translocation. However, in the transactivation assay, these combinations did not affect gene transactivation. Other POP combinations were identified here as modulators of AR-induced gene transactivation without affecting AR translocation. Thus, to fully evaluate the effect of environmental toxins on AR signalling, both types of assays need to be applied.

Ian G Mills - One of the best experts on this subject based on the ideXlab platform.

  • human blood based exposure levels of Persistent Organic Pollutant pop mixtures antagonise androgen receptor transactivation and translocation
    Environment International, 2019
    Co-Authors: Jonathan Mccomb, Hf Berntsen, Ian G Mills, Marc Muller, Karin Elisabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly
    Abstract:

    Abstract Introduction Human exposure to Persistent Organic Pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. Aim To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. Materials and methods The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. Results No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P  Conclusion Taken together, some combinations of POP mixtures can interfere with AR translocation. However, in the transactivation assay, these combinations did not affect gene transactivation. Other POP combinations were identified here as modulators of AR-induced gene transactivation without affecting AR translocation. Thus, to fully evaluate the effect of environmental toxins on AR signalling, both types of assays need to be applied.

Jonathan Mccomb - One of the best experts on this subject based on the ideXlab platform.

  • human blood based exposure levels of Persistent Organic Pollutant pop mixtures antagonise androgen receptor transactivation and translocation
    Environment International, 2019
    Co-Authors: Jonathan Mccomb, Hf Berntsen, Ian G Mills, Marc Muller, Karin Elisabeth Zimmer, Erik Ropstad, Steven Verhaegen, Lisa Connolly
    Abstract:

    Abstract Introduction Human exposure to Persistent Organic Pollutants (POPs) has been linked to genitourinary health-related conditions such as decreased sperm quality, hypospadias, and prostate cancer (PCa). Conventional risk assessment of POPs focuses on individual compounds. However, in real life, individuals are exposed to many compounds simultaneously. This might lead to combinatorial effects whereby the global effect of the mixture is different from the effect of the single elements or subgroups. POP mixtures may act as endocrine disruptors via the androgen receptor (AR) and potentially contribute to PCa development. Aim To determine the endocrine disrupting activity of a POP mixture and sub-mixtures based upon exposure levels detected in a human Scandinavian population, on AR transactivation and translocation in vitro. Materials and methods The Total POP mixture combined 29 chemicals modelled on the exposure profile of a Scandinavian population and 6 sub-mixtures: brominated (Br), chlorinated (Cl), Cl + Br, perfluorinated (PFAA), PFAA + Br, PFAA + Cl, ranging from 1/10× to 500× relative to what is found in human blood. Transactivation was measured by reporter gene assay (RGA) and translocation activity was measured by high content analysis (HCA), each using stably transfected AR model cell lines. Results No agonist activity in terms of transactivation and translocation was detected for any POP mixtures. In the presence of testosterone the Cl + Br mixture at 100× and 500× blood level antagonised AR transactivation, whereas the PFAA mixture at blood level increased AR transactivation (P  Conclusion Taken together, some combinations of POP mixtures can interfere with AR translocation. However, in the transactivation assay, these combinations did not affect gene transactivation. Other POP combinations were identified here as modulators of AR-induced gene transactivation without affecting AR translocation. Thus, to fully evaluate the effect of environmental toxins on AR signalling, both types of assays need to be applied.

Karlwerner Schramm - One of the best experts on this subject based on the ideXlab platform.

  • association of in utero Persistent Organic Pollutant exposure with placental thyroid hormones
    Endocrinology, 2018
    Co-Authors: David Hernandezmoreno, Katharina M Main, Niels E Skakkebaek, Hannu Kiviranta, Jorma Toppari, Ulla Feldtrasmussen, Heqing Shen, Karlwerner Schramm
    Abstract:

    In utero exposure to Persistent Organic Pollutants (POPs) can result in thyroid function disorder, leading to concerns about their impact on fetal and neonatal development. The associations between placental levels of various POPs and thyroid hormones (THs) were investigated. In a prospective Danish study initially established for assessing congenital cryptorchidism, 58 placenta samples were collected from mothers of boys born with (n = 28) and without (n = 30) cryptorchidism. The concentrations of polybrominated diphenyl ethers (PBDEs), polychlorinated biphenyls (PCBs), polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs), organotin chemicals (OTCs), organochlorine pesticides (OCPs), T4, T3, and rT3 were measured. The associations between placental THs and various POPs were analyzed using multiple linear regression. Five PBDEs, 35 PCBs, 14 PCDD/Fs, 3 OTCs, 25 OCPs, T4, T3, and rT3 were measured. No correlation between THs and the odds of cryptorchidism was found. Several POPs were significantly associated with THs: (1) T4 was inversely associated with BDEs 99, 100, ΣPBDE, and 2378-TeCDD, and positively associated with 1234678-HpCDF; (2) T3 was positively associated with 2378-TeCDF and 12378-PeCDF; and (3) rT3 was positively associated with PCB 81, 12378-PeCDF, and 234678-HxCDF, and inversely associated with tributyltin, ΣOTC, and methoxychlor. These results revealed that POP exposures were associated with TH levels in placenta, which may be a possible mechanism for the impacts of POP exposures on children's growth and development. This study provides new insight into the complexity of thyroid-disrupting properties of POPs. More research is needed to elucidate the biological consequences of POP exposures.

  • physiologically based Persistent Organic Pollutant accumulation in pig tissues and their edible safety differences an in vivo study
    Food Chemistry, 2012
    Co-Authors: Heqing Shen, Bernhard Henkelmann, Walter Albert Rambeck, Richard Mayer, Ulrich Wehr, Karlwerner Schramm
    Abstract:

    Abstract As one of the most important animal food sources, pigs are an important model in the assessment of human exposure to Persistent Organic Pollutants (POPs). In the present study, the distribution of the administrated polychlorodibenzo- p -dioxin/furan (PCDD/F)–polychlorinated biphenyl (PCB) mixture and polybrominated diphenyl ethers (PBDEs) in the different tissues of pigs, including liver, lung, kidney, subcutaneous fat, mesentery and muscle, for understanding the physiologically based Pollutant accumulation in these tissues and their edible safety was investigated. It was found that liver had a much higher potential to accumulate PCDD/Fs and dioxin-like Pollutants like PCB-126 than the other tissues, but it did not specifically concentrate PBDE congeners as compared to the other tissues. The different PCDD/F congeners and PCB-126 followed a similar distribution pattern in the different tissues; also the different PBDE congeners have the similar pattern in these tissues. The liver’s higher concentrating potency for dioxin-like Pollutants may result from its detoxification function, however, it can concentrate dioxin-like Pollutants but not PBDEs may suggest that it is the toxicity but not lipophilic property of these POPs dominated their accumulation in liver tissues. Also the result suggested that liver is a high-risk edible tissue for dioxin-like Pollutants. In conclusion, the present study suggested that physiologically based assessments are necessary for evaluating edible tissue safety in animal source foods.