| 1. |
- Barregård, Lars, 1948, et al.
(författare)
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Human and Methodological Sources of Variability in the Measurement of Urinary 8-Oxo-7,8-dihydro-2 '-deoxyguanosine
- 2013
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Ingår i: Antioxidants and Redox Signaling. - : Mary Ann Liebert Inc. - 1523-0864 .- 1557-7716. ; 18:18, s. 2377-2391
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Urinary 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) is a widely used biomarker of oxidative stress. However, variability between chromatographic and ELISA methods hampers interpretation of data, and this variability may increase should urine composition differ between individuals, leading to assay interference. Furthermore, optimal urine sampling conditions are not well defined. We performed inter-laboratory comparisons of 8-oxodG measurement between mass spectrometric-, electrochemical- and ELISA-based methods, using common within-technique calibrants to analyze 8-oxodG-spiked phosphate-buffered saline and urine samples. We also investigated human subject- and sample collection-related variables, as potential sources of variability. Results: Chromatographic assays showed high agreement across urines from different subjects, whereas ELISAs showed far more inter-laboratory variation and generally overestimated levels, compared to the chromatographic assays. Excretion rates in timed 'spot' samples showed strong correlations with 24 h excretion (the 'gold' standard) of urinary 8-oxodG (r(p) 0.67-0.90), although the associations were weaker for 8-oxodG adjusted for creatinine or specific gravity (SG). The within-individual excretion of 8-oxodG varied only moderately between days (CV 17% for 24 h excretion and 20% for first void, creatinine-corrected samples). Innovation: This is the first comprehensive study of both human and methodological factors influencing 8-oxodG measurement, providing key information for future studies with this important biomarker. Conclusion: ELISA variability is greater than chromatographic assay variability, and cannot determine absolute levels of 8-oxodG. Use of standardized calibrants greatly improves intra-technique agreement and, for the chromatographic assays, importantly allows integration of results for pooled analyses. If 24 h samples are not feasible, creatinine- or SG-adjusted first morning samples are recommended.
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| 2. |
- Alhamdow, Ayman, et al.
(författare)
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Fluorene exposure among PAH-exposed workers is associated with epigenetic markers related to lung cancer
- 2020
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Ingår i: Occupational and Environmental Medicine. - : BMJ. - 1351-0711 .- 1470-7926. ; 77:7, s. 488-495
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Tidskriftsartikel (refereegranskat)abstract
- Objectives Exposure to high-molecular-weight polycyclic aromatic hydrocarbons (PAHs) may cause cancer in chimney sweeps and creosote-exposed workers, however, knowledge about exposure to low-molecular-weight PAHs in relation to cancer risk is limited. In this study, we aimed to investigate occupational exposure to the low-molecular-weight PAHs phenanthrene and fluorene in relation to different cancer biomarkers. Methods We recruited 151 chimney sweeps, 19 creosote-exposed workers and 152 unexposed workers (controls), all men. We measured monohydroxylated metabolites of phenanthrene and fluorene in urine using liquid chromatography coupled to tandem mass spectrometry. We measured, in peripheral blood, the cancer biomarkers telomere length and mitochondrial DNA copy number using quantitative PCR; and DNA methylation ofF2RL3andAHRRusing pyrosequencing. Results Median PAH metabolite concentrations were higher among chimney sweeps (up to 3 times) and creosote-exposed workers (up to 353 times), compared with controls (p<0.001; adjusted for age and smoking). n-ary sumation OH-fluorene (sum of 2-hydroxyfluorene and 3-hydroxyfluorene) showed inverse associations with percentage DNA methylation ofF2RL3andAHRRin chimney sweeps (B (95% CI)=-2.7 (-3.9 to -1.5) forF2RL3_cg03636183, and -7.1 (-9.6 to -4.7) forAHRR_cg05575921: adjusted for age and smoking), but not in creosote-exposed workers. In addition, n-ary sumation OH-fluorene showed a 42% mediation effect on the inverse association between being a chimney sweep and DNA methylation ofAHRRCpG2. Conclusions Chimney sweeps and creosote-exposed workers were occupationally exposed to low-molecular-weight PAHs. Increasing fluorene exposure, among chimney sweeps, was associated with lower DNA methylation ofF2RL3andAHRR, markers for increased lung cancer risk. These findings warrant further investigation of fluorene exposure and toxicity.
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| 3. |
- De Loma, Jessica, et al.
(författare)
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Arsenic exposure and biomarkers for oxidative stress and telomere length in indigenous populations in Bolivia
- 2022
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Ingår i: Ecotoxicology and Environmental Safety. - : Elsevier BV. - 0147-6513 .- 1090-2414. ; 231
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Women living in the Bolivian Andes are environmentally exposed to arsenic, yet there is scarce information about arsenic-related effects in this region. Several biomarkers for telomere length and oxidative stress (mitochondrial DNA copy number, mtDNAcn; 8-Oxo-2'-deoxyguanosine, 8-oxo-dG; and 4-hydroxy nonenal mercapturic acid, 4-HNE-MA) have been previously linked to arsenic, and some of which are prospective biomarkers for cancer risk.OBJECTIVE AND HYPOTHESIS: To evaluate associations between arsenic exposure and telomere length, mtDNAcn, 8-oxo-dG, and 4-HNE-MA in Bolivians. Arsenic exposure was hypothesized to be positively associated with all four toxicity biomarkers, particularly in individuals with a less efficient arsenic metabolism.METHODS: The study encompassed 193 indigenous women. Arsenic exposure was assessed in urine as the sum of inorganic arsenic metabolite concentrations (U-As) measured by HPLC-HG-ICP-MS, and in whole blood as total arsenic (B-As) measured by ICP-MS. Efficiency of arsenic metabolism was evaluated by a polymorphism (rs3740393) in the main arsenic methylating gene AS3MT measured by TaqMan allelic discrimination, and by the relative fractions of urinary inorganic arsenic metabolites. Telomere length and mtDNAcn were determined in peripheral blood leukocytes by quantitative PCR, and urinary 8-oxo-dG and 4-HNE-MA by LC-MS/MS.RESULTS: U-As and B-As were associated with longer telomeres and higher mtDNAcn, particularly in women with a less efficient arsenic metabolism. Urinary 8-oxo-dG and 4-HNE-MA were positively associated with U-As, but only 4-HNE-MA was associated with B-As. Arsenic metabolism efficiency did not have a clear effect on the concentrations of either of these biomarkers.CONCLUSION: Bolivian women showed indications of arsenic toxicity, measured by four different biomarkers. Telomere length, mtDNAcn, and 4-HNE-MA were positively associated with both U-As and B-As. The association of arsenic exposure with telomere length and mtDNAcn was only present in Bolivian women with a less efficient metabolism. These findings call for additional efforts to evaluate and reduce arsenic exposure in Bolivia.
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| 4. |
- Krais, Annette M., et al.
(författare)
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Biomarkers after Controlled Inhalation Exposure to Exhaust from Hydrogenated Vegetable Oil (HVO)
- 2021
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Ingår i: International Journal of Environmental Research and Public Health. - : MDPI AG. - 1661-7827 .- 1660-4601. ; 18:12
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Tidskriftsartikel (refereegranskat)abstract
- Hydrogenated vegetable oil (HVO) is a renewable diesel fuel used to replace petroleum diesel. The organic compounds in HVO are poorly characterized; therefore, toxicological properties could be different from petroleum diesel exhaust. The aim of this study was to evaluate the exposure and effective biomarkers in 18 individuals after short-term (3 h) exposure to HVO exhaust and petroleum diesel exhaust fumes. Liquid chromatography tandem mass spectrometry was used to analyze urinary biomarkers. A proximity extension assay was used for the measurement of inflammatory proteins in plasma samples. Short-term (3 h) exposure to HVO exhaust (PM1 ~1 µg/m3 and ~90 µg/m3 for vehicles with and without exhaust aftertreatment systems, respectively) did not increase any exposure biomarker, whereas petroleum diesel exhaust (PM1 ~300 µg/m3 ) increased urinary 4-MHA, a biomarker for p-xylene. HVO exhaust from the vehicle without exhaust aftertreatment system increased urinary 4-HNE-MA, a biomarker for lipid peroxidation, from 64 ng/mL urine (before exposure) to 141 ng/mL (24 h after exposure, p < 0.001). There was no differential expression of plasma inflammatory proteins between the HVO exhaust and control exposure group. In conclusion, short-term exposure to low concentrations of HVO exhaust did not increase urinary exposure biomarkers, but caused a slight increase in lipid peroxidation associated with the particle fraction.
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| 5. |
- Rylander, Lars, et al.
(författare)
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Per-and polyfluoroalkyl substances in early pregnancy and risk for preeclampsia : A case-control study in southern Sweden
- 2020
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Ingår i: Toxics. - 2305-6304. ; 8:2
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Tidskriftsartikel (refereegranskat)abstract
- Preeclampsia is one of the most common causes of perinatal and maternal morbidity/ mortality. One suggested environmental risk factor is exposure to endocrine-disrupting pollutants such as per-and polyfluoroalkyl substances (PFAS). The present case-control study in southern Sweden aims to investigate the hypothesized association between serum concentrations of PFAS in early pregnancy and the risk of developing preeclampsia. The study included 296 women diagnosed with preeclampsia (cases) and 580 healthy pregnant women (controls). Maternal serum samples were obtained from a biobank of samples collected in early pregnancy in connection with screening for infections. Serum concentrations of perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonate (PFHxS) were analyzed using liquid chromatography-tandem-mass-spectrometry (LC/MS/MS). Among primiparous women, there were no differences in PFAS concentrations in early pregnancy between the cases and the controls whereas among multipara women, the cases had significantly higher concentrations of PFNA (median concentrations were 0.44 and 0.38 ng/mL, p = 0.04). When individual PFAS were categorized into quartiles and adjustment for potential confounders was performed, the women in the highest quartiles had no significant increased risks of developing preeclampsia as compared with women in the lowest category. In conclusion, the present study provides limited support for the hypothesized association between PFAS and preeclampsia in a population with relatively low exposure levels.
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| 6. |
- Svendsen, Kristin von Hirsch, et al.
(författare)
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Urinary 8-oxo-7, 8-dihydro-2′-deoxyguanosine concentrations after frying of bacon, a pilot study
- 2017
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Ingår i: Toxicological and Environmental Chemistry. - : Informa UK Limited. - 0277-2248 .- 1029-0486. ; 99:3, s. 525-534
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Tidskriftsartikel (refereegranskat)abstract
- Cooking fumes contain compounds that may give rise to oxidative stress and mutations when inhaled. The aim of this study was to evaluate if cooking fumes from frying of bacon induce oxidative stress by measurement of urinary 8-oxo-7,8-dihydro-2 deoxyguanosine, a marker of oxidatively damaged DNA. Three non-smoking women fried bacon for 3 h. Urine samples were taken as early morning void at the same time on four days; the morning before frying, the morning after first frying, the morning after three days of frying and one week after first urine sample. 8-Oxo-7,8-dihydro-2 deoxyguanosine, 1-hydroxypyrene and 2-hydroxyphenanthrene, metabolites of polycyclic aromatic hydrocarbons, were measured by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). 8-Oxo-7,8-dihydro-2 deoxyguanosine correlated weakly with concentrations of 1-hydroxypyrene (r = 0.31, p = 0.042), but it did not correlate with 2-hydroxyphenanthrene (r = −0.074; p = 0.64). Average urinary 8-oxo-7,8-dihydro-2 deoxyguanosine concentrations increased from the day before frying (16.3 ± 4.2 nmol/L) to the third day of frying (26.2 ± 10.2 nmol/L), although not statistically significantly. Our pilot study shows that frying of bacon may result in increased oxidative stress which further emphasises the possible carcinogenic potential of cooking fumes.
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| 7. |
- Xu, Yiyi, et al.
(författare)
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Occupational exposure to asphalt mixture during road paving is related to increased mitochondria DNA copy number : A cross-sectional study
- 2018
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Ingår i: Environmental Health: A Global Access Science Source. - : Springer Science and Business Media LLC. - 1476-069X. ; 17:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Asphalt workers are exposed to polyaromatic hydrocarbons (PAHs) from hot mix asphalt via both inhalation and dermal absorption. The use of crumb rubber modified (CRM) asphalt may result in higher exposure to PAHs and more adverse effects. Our aim is to assess occupational exposure to PAHs from conventional and CRM asphalt paving by measuring PAH metabolites in urine, and to investigate the effects on mitochondrial DNA copy number (mtDNAcn) and telomere length. Methods: We recruited 116 workers paving conventional asphalt, 51 workers paving CRM asphalt and 100 controls in Sweden, all males. A repeated-measures analysis included 31 workers paving both types of asphalt. Urine and blood samples were collected pre-working on Monday morning and post-working on Thursday afternoon after 4 days working. PAH metabolites: 1-hydroxypyrene (1-OH-PYR) and 2-hydroxyphenanthrene (2-OH-PH) were measured in urine by LC-MS/MS. Relative mtDNAcn and telomere length were measured by quantitative PCR. Results: Conventional and CRM asphalt workers showed higher 1-OH-PYR and 2-OH-PH than controls (p < 0.001 for all). Relative mtDNAcn were 0.21 units (p < 0.001) higher in conventional asphalt workers and 0.13 units (p = 0.010) higher in CRM asphalt workers compared to controls. Relative telomere length did not differ across occupational groups, but it was positively associated with increment of 2-OH-PH (β = 0.075, p = 0.037) in asphalt workers. The repeated-measures analysis showed no difference in either increment of 1-OH-PYP, or changes in effect biomarkers (mtDNAcn or telomere length) between paving with conventional and CRM asphalt. Increment of 2-OH-PH was smaller after paving with CRM asphalt. Conclusions: Road asphalt paving in open areas resulted in PAHs exposure, as shown by elevation of PAH metabolites in urine. Asphalt workers may experience oxidative stress, evidenced by alternation in mtDNAcn; however the effects could not be fully explained by exposure to PAHs from the asphalt mixture.
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