TY - JOUR
T1 - Multigenerational metabolic profiling in the Michigan PBB registry
AU - Walker, Douglas I.
AU - Marder, M. Elizabeth
AU - Yano, Yukiko
AU - Terrell, Metrecia
AU - Liang, Yongliang
AU - Barr, Dana Boyd
AU - Miller, Gary W.
AU - Jones, Dean P.
AU - Marcus, Michele
AU - Pennell, Kurt D.
N1 - Funding Information:
This work was funded by the National Institutes of Health through support to the HERCULES Exposome Research Center (award# ES019776 ), Emory’s National Exposure Assessment Laboratory (award# ES026560 ), training grant ES012870 and R01s ES12014 and ES025775 .
Publisher Copyright:
© 2019 Elsevier Inc.
PY - 2019/5
Y1 - 2019/5
N2 - Although polychlorinated biphenyls and polybrominated biphenyls are no longer manufactured the United States, biomonitoring in human populations show that exposure to these pollutants persist in human tissues. The objective of this study was to identify metabolic variations associated with exposure to 2,2'4,4’,5,5’-hexabromobiphenyl (PBB-153) and 2,2'4,4’,5,5’-hexachlorobiphenyl (PCB-153) in two generations of participants enrolled in the Michigan PBB Registry (http://pbbregistry.emory.edu/). Untargeted, high-resolution metabolomic profiling of plasma collected from 156 individuals was completed using liquid chromatography with high-resolution mass spectrometry. PBB-153 and PCB-153 levels were measured in the same individuals using targeted gas chromatography-tandem mass spectrometry and tested for dose-dependent correlation with the metabolome. Biological response to these exposures were evaluated using identified endogenous metabolites and pathway enrichment. When compared to lipid-adjusted concentrations for adults in the National Health and Nutrition Examination Survey (NHANES) for years 2003-2004, PCB-153 levels were consistent with similarly aged individuals, whereas PBB-153 concentrations were elevated (p<0.0001) in participants enrolled in the Michigan PBB Registry. Metabolic alterations were correlated with PBB-153 and PCB-153 in both generations of participants, and included changes in pathways related to catecholamine metabolism, cellular respiration, essential fatty acids, lipids and polyamine metabolism. These pathways were consistent with pathophysiological changes observed in neurodegenerative disease and included previously identified metabolomic markers of Parkinson's disease. To determine if the metabolic alterations detected in this study are replicated other cohorts, we evaluated correlation of PBB-153 and PCB-153 with plasma fatty acids measured in NHANES. Both pollutants showed similar associations with fatty acids previously linked to PCB exposure. Thus, the results from this study show metabolic alterations correlated with PBB-153 and PCB-153 exposure can be detected in human populations and are consistent with health outcomes previously reported in epidemiological and mechanistic studies.
AB - Although polychlorinated biphenyls and polybrominated biphenyls are no longer manufactured the United States, biomonitoring in human populations show that exposure to these pollutants persist in human tissues. The objective of this study was to identify metabolic variations associated with exposure to 2,2'4,4’,5,5’-hexabromobiphenyl (PBB-153) and 2,2'4,4’,5,5’-hexachlorobiphenyl (PCB-153) in two generations of participants enrolled in the Michigan PBB Registry (http://pbbregistry.emory.edu/). Untargeted, high-resolution metabolomic profiling of plasma collected from 156 individuals was completed using liquid chromatography with high-resolution mass spectrometry. PBB-153 and PCB-153 levels were measured in the same individuals using targeted gas chromatography-tandem mass spectrometry and tested for dose-dependent correlation with the metabolome. Biological response to these exposures were evaluated using identified endogenous metabolites and pathway enrichment. When compared to lipid-adjusted concentrations for adults in the National Health and Nutrition Examination Survey (NHANES) for years 2003-2004, PCB-153 levels were consistent with similarly aged individuals, whereas PBB-153 concentrations were elevated (p<0.0001) in participants enrolled in the Michigan PBB Registry. Metabolic alterations were correlated with PBB-153 and PCB-153 in both generations of participants, and included changes in pathways related to catecholamine metabolism, cellular respiration, essential fatty acids, lipids and polyamine metabolism. These pathways were consistent with pathophysiological changes observed in neurodegenerative disease and included previously identified metabolomic markers of Parkinson's disease. To determine if the metabolic alterations detected in this study are replicated other cohorts, we evaluated correlation of PBB-153 and PCB-153 with plasma fatty acids measured in NHANES. Both pollutants showed similar associations with fatty acids previously linked to PCB exposure. Thus, the results from this study show metabolic alterations correlated with PBB-153 and PCB-153 exposure can be detected in human populations and are consistent with health outcomes previously reported in epidemiological and mechanistic studies.
KW - Bioffect
KW - Biomonitoring
KW - High-resolution metabolomics
KW - Polybrominated flame retardants
KW - Polychlorinated biphenyls
UR - http://www.scopus.com/inward/record.url?scp=85061710962&partnerID=8YFLogxK
U2 - 10.1016/j.envres.2019.02.018
DO - 10.1016/j.envres.2019.02.018
M3 - Article
C2 - 30782538
AN - SCOPUS:85061710962
SN - 0013-9351
VL - 172
SP - 182
EP - 193
JO - Environmental Research
JF - Environmental Research
ER -