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.
Supplementary material and research data are available at https://doi.org/10.1016/j.envint.2019.01.003
PY - 2019/3/31
Y1 - 2019/3/31
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
UR - http://www.scopus.com/inward/record.url?scp=85059809524&partnerID=8YFLogxK
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
M3 - Article
C2 - 30641261
SN - 0160-4120
VL - 124
SP - 98
EP - 108
JO - Environment International
JF - Environment International
ER -