Dataset Information

Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

ABSTRACT: Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum samples obtained from 911 elderly subjects in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) cohort. Plasma concentrations of 30 POPs and plastic chemicals have previously been determined in the same PIVUS subjects. Linear regression analysis demonstrated that total toxic equivalence (TEQ) values and polychlorinated biphenyls (PCBs) were significantly correlated with AhR bioactivity (positively) and ATP concentration (negatively). Serum AhR bioactivities were positively associated with some PCBs, regardless of their dioxin-like properties, but only dioxin-like PCBs stimulated AhR bioactivity. By contrast, PCBs mediated a reduction in ATP content independently of their dioxin-like properties. This study suggests that AhR bioactivity and ATP concentrations in serum-treated cells may be valuable surrogate biomarkers of POP exposure and could be useful for the estimation of the effects of POPs on human health.

SUBMITTER: Park WH

PROVIDER: S-EPMC5571204 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

Park Wook Ha WH Kang Sora S Lee Hong Kyu HK Salihovic Samira S Bavel Bert van BV Lind P Monica PM Pak Youngmi Kim YK Lind Lars L

Scientific reports 20170824 1

Metabolic syndrome and mitochondrial dysfunction have been linked to elevated serum levels of persistent organic pollutants (POPs). However, it is not clear which specific POPs contribute to aryl hydrocarbon receptor (AhR)-dependent bioactivity or inhibit mitochondrial function in human subjects. Here, we measured the cumulative bioactivity of AhR ligand mixture (AhR bioactivity) and the effects on mitochondrial function (ATP concentration) in recombinant Hepa1c1c7 cells incubated with raw serum ...[more]

PMID: 28839207

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Project description:Serum concentrations of 35 ortho-substituted polychlorinated biphenyl congeners (PCBs) were measured in 765 adults from Anniston, Alabama, where PCBs were manufactured between 1929 and 1971. As part of the Anniston Community Health Survey (ACHS), demographic data, questionnaire information, and blood samples were collected from participants in 2005-2007. Forty-six percent of study participants were African-American, 70% were female, and the median age was 56 years. The median concentration of the sum of 35 PCB congeners (?PCBs) was 528 ng/g lipid, with a 90th percentile of 2,600 ng/g lipid, minimum of 17.0 ng/g lipid, and maximum of 27,337 ng/g lipid. The least square geometric mean ?PCBs was more than 2.5 times higher for African-American participants than for White participants (866 ng/g lipid vs. 331 ng/g lipid); this difference did not change materially after adjustment for age, sex, body mass index (BMI) and current smoking. In spite of large differences in absolute PCB levels, relative contributions of individual congeners to ?PCBs were quite similar between race groups. Nevertheless, while percent contributions to ?PCBs for most of the most abundant penta- to heptachlorobiphenyls were higher among African-Americans, the percentages were higher in Whites for the lower-chlorinated PCBs 28 and 74 and for octa- to decachlorinated PCBs. No major differences were observed in geometric mean ?PCBs between women and men when adjusted for age, race, BMI and current smoking (516 ng/g lipid vs. 526 ng/g lipid). Principal component analysis revealed groups of co-varying congeners that appear to be determined by chlorine substitution patterns. These congener groupings were similar between ACHS participants and the National Health and Nutrition Examination Survey (NHANES) 2003-04 sample of the general United States population, despite ACHS participants having serum concentrations of ?PCBs two to three times higher than those in comparable age and race groups from NHANES.

Project description:BackgroundIn 1973-1974, Michigan residents were exposed to polybrominated biphenyls (PBBs) through an accidental contamination of the food supply. Residents were enrolled in a registry assembled after the incident, and they and their children participated in follow-up studies to assess subsequent health outcomes.ObjectivesWe evaluated associations between serum PBBs and polychlorinated biphenyls (PCBs) and markers of thyroid function among Michigan adults.MethodsSerum concentrations of four PBB and four PCB congeners were measured at least once in 753 adults, including 79 women who participated in a 2004-2006 study and 683 women and men with follow-up during 2012-2015. Participants completed questionnaires on health conditions (including physician-diagnosed thyroid disease), behaviors, and demographics. Thyroid hormones were measured in a subset without thyroid disease (n=551). In multivariable linear regression models, PBB and PCB congener concentrations, on both the volume (nanogram/milliliter) and lipid (nanogram/gram lipid) basis, were assessed in relation to thyroid hormones. Logistic regression models were used to estimate associations between serum PBBs and PCBs and thyroid disease.ResultsThyroid disease was common (18% overall; 25% among women). Among women, all odds ratios (ORs) for PBB-153 and thyroid disease were positive for quintiles above the reference level, but estimates were imprecise and were without a monotonic increase. For an interquartile range (IQR) increase in PBB-153 (0.43?ng/mL), the OR?(any?thyroid?disease)=1.12; (95% CI: 0.83, 1.52) (n=105?cases); for hypothyroidism, OR=1.35 (95% CI: 0.86, 2.13) (n=49?cases). There were 21 cases of thyroid disease in men [OR=0.69 (95% CI: 0.33); 1.44 for an IQR increase (0.75?ng/mL) in serum PBB-153]. PCB congeners were statistically significantly associated with greater total and free thyroxine and total triiodothyronine among women and with total and free triiodothyronine among men in lipid-standardized models.ConclusionsWe found some evidence to support associations of PBBs and PCBs with thyroid disease and thyroid hormone levels. https://doi.org/10.1289/EHP1302.

Dataset Information

Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

Publications

Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs).

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