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Stubleski, J., Kukucka, P., Salihovic, S., Lind, P. M., Lind, L. & Kärrman, A. (2018). A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction. Journal of Chromatography A, 1546, 18-27
Open this publication in new window or tab >>A method for analysis of marker persistent organic pollutants in low-volume plasma and serum samples using 96-well plate solid phase extraction
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2018 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1546, p. 18-27Article in journal (Refereed) Published
Abstract [en]

The objective of this study was to develop and validate a 96-well plate solid phase extraction method for analysis of 23 lipophilic persistent organic pollutants (POPs) in low-volume plasma and serum samples which is applicable for biomonitoring and epidemiological studies. The analysis of selected markers for internal exposure: 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and polybrominated diphenylether 47 (BDE 47) was evaluated by comparing two SPE sorbents and GC-HRMS or GC-MS/MS detection. The final method extracted 23 POPs from 150 μL of serum and plasma using a 96-well extraction plate containing 60 mg Oasis HLB sorbent per well prior to GC-HRMS magnetic sector analysis. The extraction method was applied to 40 plasma samples collected for an epidemiological study. The recovery of selected POPs ranged from 31% to 63% (n = 48), and detection limits ranged from 2.2 to 45 pg/mL for PCBs, 4.2 to 167 pg/mL for OCPs, 7.8 pg/mL for OCDD and 6.1 pg/mL for BDE 47. This method showed good precision with relative standard deviations of selected POP concentrations in quality control samples (n = 48) ranging from 11% to 25%. The trueness was determined with standard reference material serum (n = 48) and the deviation from certified values ranged from 1 to 27%. Of the 23 POPs analyzed, 18 were detected in 43% to 100% of plasma samples collected for the epidemiological study. The method showed good robustness with low inter-well plate variation (11-31%) determined by twelve 96-well plate extractions, and can extract 96 samples, including quality controls and procedural blanks in 2-3 days. Comparison with GC-MS/MS analysis showed that similar concentrations (within 0.5% to 30%) of most POPs could be obtained with GC-APCI-MS/MS. Larger deviations were observed for PCB 194 (60%) and trans-nonachlor (43%). The developed method produces accurate concentrations of low-level marker POPs in plasma and serum, providing a suitable high-throughput sample preparation procedure for biomonitoring and epidemiological studies involving large sample size and limited sample volume. GC-HRMS was chosen over GC-MS/MS, however the latter showed promising results, and could be used as an alternative to GC-HRMS analysis for most POPs.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
High-throughput SPE, Persistent organic pollutants, GC-HRMS, APCI-MS/MS
National Category
Analytical Chemistry
Identifiers
urn:nbn:se:oru:diva-66713 (URN)10.1016/j.chroma.2018.02.057 (DOI)000430766800003 ()29510870 (PubMedID)2-s2.0-85042642069 (Scopus ID)
Funder
Swedish Research Council Formas, 216-2013-478
Note

Funding Agency:

RECETOX Research Infrastructure  LM2015051  CZ.02.1.01/0.0/0.0/16_013/0001761

Available from: 2018-04-23 Created: 2018-04-23 Last updated: 2018-05-14Bibliographically approved
Salihovic, S., Stubleski, J., Kärrman, A., Larsson, A., Fall, T., Lind, L. & Lind, P. M. (2018). Changes in markers of liver function in relation to changes in perfluoroalkyl substances: A longitudinal study. Environment International, 117, 196-203
Open this publication in new window or tab >>Changes in markers of liver function in relation to changes in perfluoroalkyl substances: A longitudinal study
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2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 117, p. 196-203Article in journal (Refereed) Published
Abstract [en]

Background: While it is known that perfluoroalkyl substances (PFASs) induce liver toxicity in experimental studies, the evidence of an association in humans is inconsistent.

Objective: The main aim of the present study was to examine the association of PFAS concentrations and markers of liver function using panel data.

Methods: We investigated 1002 individuals from Sweden (50% women) at ages 70, 75 and 80 in 2001-2014. Eight PFASs were measured in plasma using isotope dilution ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS). Bilirubin and hepatic enzymes alanine aminotransferase (ALT), alkaline phosphatase (ALP), and gamma-glutamyltransferase (GGT) were determined in serum using an immunoassay methodology. Mixed-effects linear regression models were used to examine the relationship between the changes in markers of liver function and changes in PFAS levels.

Results: The changes in majority of PFAS concentrations were positively associated with the changes in activity of ALT, ALP, and GGT and inversely associated with the changes in circulating bilirubin after adjustment for gender and the time-updated covariates LDL- and HDL-cholesterol, serum triglycerides, BMI, statin use, smoking, fasting glucose levels and correction for multiple testing. For example, changes in perfluorononanoic acid (PFNA) were associated with the changes liver function markers beta(BILIRUBIN) = -1.56, 95% confidence interval (CI) -1.93 to -1.19, beta(ALT)= 0.04, 95% CI 0.03-0.06, and beta(ALP)= 0.11, 95% CI 0.06-0.15.

Conclusion: Our longitudinal assessment established associations between changes in markers of liver function and changes in plasma PFAS concentrations. These findings suggest a relationship between low-dose background PFAS exposure and altered liver function in the general population.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Epidemiology, Liver function markers, PFAS, ALT, Bilirubin, PFNA
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-67003 (URN)10.1016/j.envint.2018.04.052 (DOI)000436573400023 ()29754000 (PubMedID)2-s2.0-85046747241 (Scopus ID)
Funder
Swedish Research Council Formas, 2007-2047 2013-478 2015-756
Available from: 2018-05-24 Created: 2018-05-24 Last updated: 2018-07-27Bibliographically approved
Lind, P. M., Salihovic, S., Stubleski, J., Kärrman, A. & Lind, L. (2018). Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study. Environmental health, 17, Article ID 59.
Open this publication in new window or tab >>Changes in plasma levels of perfluoroalkyl substances (PFASs) are related to increase in carotid intima-media thickness over 10 years - a longitudinal study
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2018 (English)In: Environmental health, ISSN 1476-069X, E-ISSN 1476-069X, Vol. 17, article id 59Article in journal (Refereed) Published
Abstract [en]

Background: It has previously been reported that the environmental contaminants perfluoroalkyl substances (PFASs) are linked to atherosclerosis in cross-sectional studies. Since cross-sectional studies could be subject to reverse causation, the purpose of this study was to analyze if the longitudinal changes in PFASs during a 10-year follow-up were related to the change in carotid artery intima-media thickness (IMT, ultrasound) during the same period.

Methods: In the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, 1016 individuals were investigated at age 70; 826 of them were reinvestigated at age 75 and 602 at age 80 years. Eight different PFASs were measured in plasma by ultra-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS), and IMT was measured at all three time points. Random-effects mixed regression models were used to examine the associations over time.

Results: IMT increased 0.058 mm during the 10-year period (p <0.0001). Following adjustment for baseline values of PFASs (age 70) and sex, the changes in plasma levels of 6 of the 8 measured PFASs were significantly related to the change in IMT over the 10-year follow-up period in a positive fashion (p <0.0062 using Bonferroni correction for 8 tests). Further adjustment for traditional cardiovascular (CV) risk factors (HDL and LDL cholesterol, smoking, systolic blood pressure, statin use, fasting glucose and serum triglycerides) affected these relationships only marginally.

Conclusion: The change in plasma levels of several PFASs during 10 years was positively related to increase in IMT seen during the same period, giving prospective evidence that PFASs might interfere with the atherosclerotic process.

Place, publisher, year, edition, pages
BMC, 2018
Keywords
Atherosclerosis, Longitudinal, Perfluoroalkyl substances (PFASs), Elderly, Epidemiology, IMT
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-68134 (URN)10.1186/s12940-018-0403-0 (DOI)000437299700002 ()29970113 (PubMedID)2-s2.0-85049455829 (Scopus ID)
Funder
Swedish Research Council Formas, 2007-2047
Available from: 2018-07-26 Created: 2018-07-26 Last updated: 2018-07-26Bibliographically approved
Lind, P. M., Salihovic, S. & Lind, L. (2018). High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis. Environment International, 113, 109-113
Open this publication in new window or tab >>High plasma organochlorine pesticide levels are related to increased biological age as calculated by DNA methylation analysis
2018 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 113, p. 109-113Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Organochlorine pesticides (OCPs) have been shown in the experimental setting to alter DNA methylation. Since DNA methylation changes during the life-span, formulas have been presented to calculate "DNA methylation age" as a measure of biological age.

OBJECTIVES: We aimed to investigate if circulating levels of three OCPs were related to increased DNA methylation age METHODS: 71CpG DNA methylation age (Hannum formula) was calculated based on data from the Illumina 450 k Bead Methylation chip in 1000 subjects in the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS) study (50% women, all aged 70 years at the examination). The difference between DNA methylation age and chronological age was calculated (DiffAge). 2,2-bis (4-chlorophenyl)-1,1-dichloroethene (p,p'-DDE), hexachlorobenzene (HCB), and transnonachlor (TNC) levels were measured in plasma by high-resolution gas chromatography coupled mass spectrometry (HRGC-HRMS).

RESULTS: Increased p,p'-DDE and TNC, but not HCB, levels were related to increased DiffAge both in sex and BMI-adjusted models, as well as in multiple adjusted models (sex, education level, exercise habits, smoking, energy and alcohol consumption and BMI) (p = 0.0051 and p = 0.011, respectively). No significant interactions between the OCPs and sex or BMI regarding DiffAge were found.

CONCLUSION: In this cross-sectional study, increased levels of two out of three OCPs were related to increased DNA methylation age, further suggesting negative health effects in humans of these widespread environmental contaminants.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
Biological age, Epidemiology, Methylation, Organochlorine pesticides (OCPs), Transnonachlor, p, p′-DDE
National Category
Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-66468 (URN)10.1016/j.envint.2018.01.019 (DOI)000428976700013 ()29421399 (PubMedID)2-s2.0-85041677797 (Scopus ID)
Funder
Swedish Research Council Formas, 2007-2047, 942-2015-756, 216-2013-478
Available from: 2018-04-13 Created: 2018-04-13 Last updated: 2018-07-26Bibliographically approved
Jayasinghe, S., Lind, L., Salihovic, S., Larsson, A. & Lind, P. M. (2018). High serum levels of p,p'-DDE are associated with an accelerated decline in GFR during 10 years follow-up. Science of the Total Environment, 644, 371-374, Article ID S0048-9697(18)32495-1.
Open this publication in new window or tab >>High serum levels of p,p'-DDE are associated with an accelerated decline in GFR during 10 years follow-up
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2018 (English)In: Science of the Total Environment, ISSN 0048-9697, E-ISSN 1879-1026, Vol. 644, p. 371-374, article id S0048-9697(18)32495-1Article in journal (Refereed) Epub ahead of print
Abstract [en]

Over the past 20 years, the global incidence of chronic kidney disease (CKD) has been increasing and organochlorine pesticides (such as DDT) is a suspected etiological factor. The present study examines the associations between low level background exposure to p,p'-DDE (1-dichloro-2,2-bis (p-chlorophenyl) ethylene), the main DDT metabolite, and kidney function during a 10-year follow-up. Data was analysed from the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (n = 1016, 50% women, all aged 70 years). Serum levels of p,p'-DDE was measured by gas chromatography coupled to high-resolution mass spectrometry (GC/HRMS) at baseline (i.e. age of 70 years). Glomerular filtration rate (GFR) was estimated using serum creatinine and cystatin C at 70, 75 and 80 years of age. A significant decline in GFR was seen during the 10-year follow-up (-24 ml/min/1.73 m2, p < 0.0001). A significant negative interaction was seen between baseline p,p'-DDE levels and change in GFR over time (p < 0.0001) following adjustment for sex, systolic blood pressure, diabetes, BMI, smoking and education level at age 70. Subjects with the lowest levels of p,p'-DDE levels at age 70 showed the lowest decline in GFR over 10 years, while subjects with the highest p,p'-DDE levels showed the greatest decline. Baseline levels of p,p'-DDE were related to an accelerated reduction in GFR over 10 years suggesting a nephrotoxic effect of DDT/p,p'-DDE. These findings support a potential role for DDT in the epidemic of CKD of unknown etiology (CKDu) in agricultural communities of Sri Lanka and Central America where DDT was previously used.

Place, publisher, year, edition, pages
Elsevier, 2018
Keywords
DDE, DDT, Kidney function, Organochlorine pesticides
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-68367 (URN)10.1016/j.scitotenv.2018.07.020 (DOI)29981985 (PubMedID)
Available from: 2018-08-07 Created: 2018-08-07 Last updated: 2018-08-07Bibliographically approved
Stubleski, J., Lind, L., Salihovic, S., Lind, P. M. & Kärrman, A. (2018). Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women. Environmental Research, 165, 193-200
Open this publication in new window or tab >>Longitudinal changes in persistent organic pollutants (POPs) from 2001 to 2009 in a sample of elderly Swedish men and women
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2018 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 165, p. 193-200Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Prospective cohort studies evaluating the temporal trends of background-level persistent organic pollutants (POPs) and their potential negative health effects in humans are needed.

OBJECTIVE: The objectives of this study are to examine the five year longitudinal trend in chlorinated and brominated (Cl/Br) POP concentrations in a sample of elderly individuals and to investigate the relationship between gender, changes in body weight, plasma lipid levels and POP concentrations.

METHODS: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study, plasma samples were collected from the same individuals over a 5 year period. Originally 992 subjects (all aged 70) were sampled between 2001 and 2004 and 814 returning subjects (all aged 75) were sampled again from 2006 to 2009. Plasma concentrations of 16 polychlorinated biphenyls (PCBs), 5 organochlorine pesticides (OCPs), octachlorinated dibenzo-p-dioxin (OCDD), and one polybrominated diphenylether (BDE 47) were determined using high-throughput 96-well plate solid phase extraction and gas chromatography-high resolution mass spectrometry (GC-HRMS).

RESULTS: During the 5-year follow-up, plasma concentrations of all POPs significantly decreased (p < 0.00001). Median reductions ranged from 4% (PCB105) to 45% (PCB 99), with most reductions being in the 30-40% range. For most POPs, a larger decline was seen in men than in women. The relationship between the weight change and change in POP concentrations was generally negative, but a positive relationship between lipid levels and POP concentrations when expressed as wet-weight was observed. In general, similar changes in POP concentrations and their relationships to body weight were observed regardless of using either wet-weight (pg/mL) or lipid-normalized (ng/g lipid) concentrations.

CONCLUSION: In this longitudinal cohort study, gender and minor, but varying changes in body weight and lipid levels greatly influenced the individual-based changes in POP concentrations. In general, our findings suggest that men and women with larger decreases in body weight and greater increases in lipid levels have the slowest decline in body burden of POPs. Based on the results from this study, either wet-weight or lipid normalized concentrations can be used to determine the percent change in POP concentrations and their relationships to physiological changes and differences.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Persistent organic pollutants, Longitudinal trend, PIVUS cohort, Body weight, Plasma lipids
National Category
Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-66867 (URN)10.1016/j.envres.2018.04.009 (DOI)000437551200021 ()29715601 (PubMedID)2-s2.0-85046341057 (Scopus ID)
Funder
Swedish Research Council, K2009-64X-21031-01-3Swedish Research Council Formas, 216-2007-2047
Available from: 2018-05-21 Created: 2018-05-21 Last updated: 2018-07-25Bibliographically approved
La Merrill, M. A., Lind, P. M., Salihovic, S., van Bavel, B. & Lind, L. (2018). The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity. Environmental Research, 160, 541-546
Open this publication in new window or tab >>The association between p,p'-DDE levels and left ventricular mass is mainly mediated by obesity
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2018 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 160, p. 541-546Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND OBJECTIVES: The pesticide metabolite p,p'-DDE has been associated with left ventricular (LV) mass and known risk factors for LV hypertrophy in humans and in experimental models. We hypothesized that the associations of p,p'-DDE with LV hypertrophy risk factors, namely elevated glucose, adiposity and hypertension, mediate the association of p,p'-DDE with LV mass.

METHODS: p,p'-DDE was measured in plasma from 70-year-old subjects (n = 988) of the Prospective Study of the Vasculature in Uppsala Seniors (PIVUS). When these subjects were 70-, 75- and 80- years old, LV characteristics were measured by echocardiography, while fasting glucose, body mass index (BMI) and blood pressure were assessed with standard clinical techniques.

RESULTS: We found that p,p'-DDE levels were associated with increased fasting glucose, BMI, hypertension and LV mass in separate models adjusted for sex. Structural equation modeling revealed that the association between p,p'-DDE and LV mass was almost entirely mediated by BMI (70%), and also by hypertension (19%).

CONCLUSION: The obesogenic effect of p,p'-DDE is a major determinant responsible for the association of p,p'-DDE with LV mass.

Place, publisher, year, edition, pages
Academic Press, 2018
Keywords
Glucose, Hypertension, Left ventricular hypertrophy, Obesity, P, p′-DDE
National Category
Cardiac and Cardiovascular Systems Occupational Health and Environmental Health
Identifiers
urn:nbn:se:oru:diva-62384 (URN)10.1016/j.envres.2017.10.031 (DOI)000417548600058 ()29106953 (PubMedID)2-s2.0-85032660018 (Scopus ID)
Funder
Swedish Research Council, 2012-2407Swedish Research Council Formas, 2007-2047
Note

Funding agencies:

USDA National Institute of Food and Agriculture 1002182

National Institutes of Health ES019919 ES023513

Available from: 2018-01-02 Created: 2018-01-02 Last updated: 2018-01-13Bibliographically approved
Lind, P. M., Salihovic, S., van Bavel, B. & Lind, L. (2017). Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis. Environmental Research, 152, 157-164
Open this publication in new window or tab >>Circulating levels of perfluoroalkyl substances (PFASs) and carotid artery atherosclerosis
2017 (English)In: Environmental Research, ISSN 0013-9351, E-ISSN 1096-0953, Vol. 152, p. 157-164Article in journal (Refereed) Published
Abstract [en]

Background and objective: During recent years, some persistent organic pollutants (POPs) have been linked to atherosclerosis. One group of POPs, the poly- and perfluoroalkyl substances (PFASs) have not been investigated with regard to atherosclerotic plaques.

Methods: Carotid artery atherosclerosis was assessed by ultrasound in 1016 subjects aged 70 years in the Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Eight PFASs were detected in >75% of participants' plasma by ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).

Results: No significant linear associations were observed between the PFASs and intima-media thickness (IMT), or the echogenicity in the intima-media complex (IM-GSM, a marker of lipid infiltration in the artery) when men and women were analyzed together. Neither was occurrence of carotid plaques related to PFASs levels. However, highly significant interactions were observed between some PFASs and sex regarding both IM-GSM and plaque prevalence. Perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroundecanoic acid (PFUnDA), were all related to IM-GSM in a positive fashion in women (p=0.002-0.003), while these relationships were negative in men. The levels of PFUnDA were significantly related to carotid plaque in women (OR 1.59, 95%CI 1.03-2.43, p=0.03), but not in men (OR 0.93, 95%CI 0.62-1.42, p=0.75).

Conclusions: In this cross-sectional study, a pronounced gender difference was observed regarding associations between some PFASs, especially the long-chain PFUnDA, and markers of atherosclerosis, with more pronounced relationships found in women. These findings suggest a sex-specific role for PFASs in atherosclerosis.

Place, publisher, year, edition, pages
Elsevier, 2017
Keywords
Atherosclerosis, Atherosclerotic plaques, Poly- and perfluoroalkyl substances (PFASs)
National Category
Occupational Health and Environmental Health Environmental Sciences
Identifiers
urn:nbn:se:oru:diva-54418 (URN)10.1016/j.envres.2016.10.002 (DOI)000389684600020 ()27771570 (PubMedID)2-s2.0-84992396745 (Scopus ID)
Funder
Swedish Research Council Formas
Available from: 2017-01-11 Created: 2017-01-10 Last updated: 2018-07-30Bibliographically approved
Lind, L., Ng, E., Ingelsson, E., Lindgren, C., Salihovic, S., van Bavel, B., . . . Lind, P. M. (2017). Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample. Environment International, 98, 212-218
Open this publication in new window or tab >>Genetic and methylation variation in the CYP2B6 gene is related to circulating p,p '-dde levels in a population-based sample
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2017 (English)In: Environment International, ISSN 0160-4120, E-ISSN 1873-6750, Vol. 98, p. 212-218Article in journal (Refereed) Published
Abstract [en]

Objectives: Since the metabolism of the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) is not fully known in humans, we evaluated if circulating levels of a major breakdown product of DDT, p,p'-DDE, were related to genome-wide genetic and methylation variation in a population-based sample.

Methods: In the population-based Prospective Investigation of the Vasculature in Uppsala Seniors (PIVUS) study (1016 subjects all aged 70), circulating levels of p, p'-DDE were analyzed by high-resolution chromatography coupled to high-resolution mass spectrometry (HRGC/HRMS). Genetic variants were genotyped and imputed (1000 Genomes reference, March 2012 release). Methylation sites were assayed using the Illumina HumanMethylation450 array in whole blood. A genome-wide association study (GWAS) approach was applied.

Results: Evidence for genome-wide significant association with p,p'-DDE levels was observed only for a locus at chromosome 19 corresponding to the CYP2B6 gene (lead SNP rs7260538). Subjects being homozygote for the G allele showed a median level of 472 ng/g lipid, while the corresponding level for those being homozygote for the T allelewas 192 ng/g lipid (p= 1.5x10(-31)). An analysis conditioned on the lead SNP disclosed a distinct signal in the same gene (rs7255374, position chr19: 41520351; p= 2.2 x 10(-8)). A whole-genome methylation analysis showed one significant relationship vs. p,p'-DDE levels (p= 6.2 x 10(-9)) located 7 kb downstreamthe CYP2B6 gene (cg27089200, position chr19: 41531976). This CpG-sitewas also related to the lead SNP (p = 3.8 x 10(-35)), but mediated only 4% of the effect of the lead SNP on p, p'-DDE levels.

Conclusion: Circulating levels of p, p'-DDE were related to genetic variation in the CYP2B6 gene in the general elderly population. DNA methylation in this gene is not closely linked to the p, p'-DDE levels.

Place, publisher, year, edition, pages
Oxford, United Kingdom: Elsevier, 2017
Keywords
GWAS, CYP2B6, DDE, Metabolism, Methylation
National Category
Environmental Sciences
Research subject
Enviromental Science
Identifiers
urn:nbn:se:oru:diva-54308 (URN)10.1016/j.envint.2016.11.010 (DOI)000389913500025 ()2-s2.0-84997637282 (Scopus ID)
Funder
Swedish Research Council Formas, 216-2012-475
Available from: 2017-01-10 Created: 2017-01-09 Last updated: 2018-07-30Bibliographically approved
Park, W. H., Kang, S., Lee, H. K., Salihovic, S., van Bavel, B., Lind, P. M., . . . Lind, L. (2017). Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs). Scientific Reports, 7, Article ID 9383.
Open this publication in new window or tab >>Relationships between serum-induced AhR bioactivity or mitochondrial inhibition and circulating polychlorinated biphenyls (PCBs)
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2017 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 7, article id 9383Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Nature Publishing Group, 2017
National Category
Pharmacology and Toxicology
Identifiers
urn:nbn:se:oru:diva-60719 (URN)10.1038/s41598-017-09774-1 (DOI)000408441600107 ()28839207 (PubMedID)2-s2.0-85028042887 (Scopus ID)
Funder
Swedish Research Council Formas
Note

Funding Agency:

Korean Health Technology R&D Project, Ministry of Health Welfare  HI14C2700

Available from: 2017-09-11 Created: 2017-09-11 Last updated: 2018-01-13Bibliographically approved
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