Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males

Panagiotis Filis (Corresponding Author), Natasha Walker, Linda Robertson, Emily Eaton-Turner, Lauma Ramona, Michelle Bellingham, Maria R. Amezaga, Zulin Zhang, Beatrice Mandon-Pepin, Neil P. Evans, Richard M. Sharpe, Corinne Cotinot, William D. Rees, Peter O'Shaughnessy, Paul A. Fowler

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Abstract

Background. The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. Objectives. The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. Methods. Four groups of sheep (n=10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography / tandem mass spectroscopy. Results. Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. Conclusions. Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.
Original languageEnglish
Pages (from-to)98-108
Number of pages10
JournalEnvironment International
Volume124
Early online date11 Jan 2019
DOIs
Publication statusPublished - Mar 2019

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cancer
lipid
fertilizer
protein
culling
PCB
detoxification
sheep
PAH
plasma
infertility
sewage sludge
exposure
marker
chemical
homeostasis
xenobiotics
RNA
liquid chromatography
pasture

Keywords

  • environmental exposure
  • PAH
  • sewage sludge
  • sheep
  • liver
  • proteomics
  • Environmental exposure
  • Liver
  • Proteomics
  • Sheep
  • Sewage sludge

ASJC Scopus subject areas

  • Environmental Science(all)

Cite this

Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males. / Filis, Panagiotis (Corresponding Author); Walker, Natasha; Robertson, Linda; Eaton-Turner, Emily; Ramona, Lauma; Bellingham, Michelle; Amezaga, Maria R.; Zhang, Zulin ; Mandon-Pepin, Beatrice; Evans, Neil P.; Sharpe, Richard M.; Cotinot, Corinne; Rees, William D.; O'Shaughnessy, Peter; Fowler , Paul A.

In: Environment International, Vol. 124, 03.2019, p. 98-108.

Research output: Contribution to journalArticle

Filis, P, Walker, N, Robertson, L, Eaton-Turner, E, Ramona, L, Bellingham, M, Amezaga, MR, Zhang, Z, Mandon-Pepin, B, Evans, NP, Sharpe, RM, Cotinot, C, Rees, WD, O'Shaughnessy, P & Fowler , PA 2019, 'Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males', Environment International, vol. 124, pp. 98-108. https://doi.org/10.1016/j.envint.2019.01.003
Filis, Panagiotis ; Walker, Natasha ; Robertson, Linda ; Eaton-Turner, Emily ; Ramona, Lauma ; Bellingham, Michelle ; Amezaga, Maria R. ; Zhang, Zulin ; Mandon-Pepin, Beatrice ; Evans, Neil P. ; Sharpe, Richard M. ; Cotinot, Corinne ; Rees, William D. ; O'Shaughnessy, Peter ; Fowler , Paul A. / Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males. In: Environment International. 2019 ; Vol. 124. pp. 98-108.
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title = "Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males",
abstract = "Background. The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. Objectives. The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. Methods. Four groups of sheep (n=10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography / tandem mass spectroscopy. Results. Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. Conclusions. Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.",
keywords = "environmental exposure, PAH, sewage sludge, sheep, liver, proteomics, Environmental exposure, Liver, Proteomics, Sheep, Sewage sludge",
author = "Panagiotis Filis and Natasha Walker and Linda Robertson and Emily Eaton-Turner and Lauma Ramona and Michelle Bellingham and Amezaga, {Maria R.} and Zulin Zhang and Beatrice Mandon-Pepin and Evans, {Neil P.} and Sharpe, {Richard M.} and Corinne Cotinot and Rees, {William D.} and Peter O'Shaughnessy and Fowler, {Paul A.}",
note = "This work was supported by the SRF Academic Scholarship Award 2013 (to PAF, PJOS, PF), the Wellcome Trust (080388 to PAF, CC, SMR, RMS, NPE) and the European Community’s Seventh Framework Programme (FP7 ⁄ 2007-2013 to PAF, SMR, CC) under grant agreement no 212885. The authors would like to thank Ms Margaret Fraser and the Proteomics Core Facility at the University of Aberdeen and Ms Carol E. Kyle and as Dr Stewart Rhind (deceased) at James Hutton Institute, Aberdeen, for their important contributions to this study.",
year = "2019",
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language = "English",
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pages = "98--108",
journal = "Environment International",
issn = "0160-4120",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Long-term exposure to chemicals in sewage sludge fertilizer alters liver lipid content in females and cancer marker expression in males

AU - Filis, Panagiotis

AU - Walker, Natasha

AU - Robertson, Linda

AU - Eaton-Turner, Emily

AU - Ramona, Lauma

AU - Bellingham, Michelle

AU - Amezaga, Maria R.

AU - Zhang, Zulin

AU - Mandon-Pepin, Beatrice

AU - Evans, Neil P.

AU - Sharpe, Richard M.

AU - Cotinot, Corinne

AU - Rees, William D.

AU - O'Shaughnessy, Peter

AU - Fowler , Paul A.

N1 - This work was supported by the SRF Academic Scholarship Award 2013 (to PAF, PJOS, PF), the Wellcome Trust (080388 to PAF, CC, SMR, RMS, NPE) and the European Community’s Seventh Framework Programme (FP7 ⁄ 2007-2013 to PAF, SMR, CC) under grant agreement no 212885. The authors would like to thank Ms Margaret Fraser and the Proteomics Core Facility at the University of Aberdeen and Ms Carol E. Kyle and as Dr Stewart Rhind (deceased) at James Hutton Institute, Aberdeen, for their important contributions to this study.

PY - 2019/3

Y1 - 2019/3

N2 - Background. The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. Objectives. The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. Methods. Four groups of sheep (n=10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography / tandem mass spectroscopy. Results. Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. Conclusions. Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.

AB - Background. The increased incidence of diseases, including metabolic syndrome and infertility, may be related to exposure to the mixture of chemicals, which are ubiquitous in the modern environment (environmental chemicals, ECs). Xeno-detoxification occurs within the liver which is also the source of many plasma proteins and growth factors and plays an important role in the regulation of homeostasis. Objectives. The objective of this study was to investigate the effects of ECs on aspects of liver function, in a well characterized ovine model of exposure to a real-life EC mixture. Methods. Four groups of sheep (n=10-12/sex/treatment) were maintained long-term on control or sewage sludge-fertilized pastures: from conception to culling at 19 months of age in females and from conception to 7 months of age and thereafter in control plots until culling at 19 months of age in males. Environmental chemicals were measured in sheep livers and RNA and protein extracts were assessed for exposure markers. Liver proteins were resolved using 2D differential in-gel electrophoresis and differentially expressed protein spots were identified by liquid chromatography / tandem mass spectroscopy. Results. Higher levels of polycyclic aromatic hydrocarbons (PAHs) and lower levels of polychlorinated biphenyls (PCBs) in the livers of control males compared to control females indicated sexually dimorphic EC body burdens. Increased levels of the PAHs Benzo[a]anthracene and chrysene and reduced levels of PCB 153 and PCB 180 were observed in the livers of continuously exposed females. EC exposure affected xenobiotic and detoxification responses and the liver proteome in both sexes and included major plasma secreted and blood proteins, and metabolic enzymes whose pathway analysis predicted dysregulation of cancer-related pathways and altered lipid dynamics. The latter were confirmed by a reduction in total lipids in female livers and up-regulation of cancer-related transcript markers in male livers respectively by sewage sludge exposure. Conclusions. Our results demonstrate that chronic exposure to ECs causes major physiological changes in the liver, likely to affect multiple systems in the body and which may predispose individuals to increased disease risks.

KW - environmental exposure

KW - PAH

KW - sewage sludge

KW - sheep

KW - liver

KW - proteomics

KW - Environmental exposure

KW - Liver

KW - Proteomics

KW - Sheep

KW - Sewage sludge

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UR - http://www.mendeley.com/research/longterm-exposure-chemicals-sewage-sludge-fertilizer-alters-liver-lipid-content-females-cancer-marke

U2 - 10.1016/j.envint.2019.01.003

DO - 10.1016/j.envint.2019.01.003

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VL - 124

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EP - 108

JO - Environment International

JF - Environment International

SN - 0160-4120

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