| 1. |
- Ameer, S. S., et al.
(författare)
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Exposure to inorganic arsenic and mitochondrial DNA copy number and telomere length in peripheral blood
- 2016
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Ingår i: Arsenic Research and Global Sustainability - Proceedings of the 6th International Congress on Arsenic in the Environment, AS 2016. - 9781138029415 ; , s. 450-452
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Konferensbidrag (refereegranskat)abstract
- Exposure to inorganic arsenic (iAs) is a risk factor for cancer. Alterations in mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) have been associated with cancer risk. Two Argentinean groups were studied: A) Puna area of Andes and B) Chaco. Arsenic exposure was assessed as the sum of arsenic metabolites (iAs, MMA, and DMA) in urine (U-As) using HPLC-HG-ICPMS. MtDNAcn, TL, and genotype of the arsenic-methylating gene AS3MT were determined in blood by real-timePCR. The Chaco participants had less-efficient metabolism, with higher%iAs and%MMA in urine, and lower frequency of the efficient-metabolizing AS3MT haplotype. U-As was associated with increased mtDNAcn in Chaco but not in Andes. U-As was associated with longer TL in Chaco, but less so in Andes. Individuals with%iAs>median showed significantly higher mtDNAcn and TL in both groups. Arsenic was associated with increased mtDNAcn and TL, particularly in individuals with less-efficient arsenic metabolism, who might have increased risk for arsenic-related cancer.
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| 2. |
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| 3. |
- Broberg, K, et al.
(författare)
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Arsenic exposure in early pregnancy alters genome-wide DNA methylation in cord blood, particularly in boys.
- 2014
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Ingår i: Journal of Developmental Origins of Health and Disease. - 2040-1752. ; 5:4, s. 288-298
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Tidskriftsartikel (refereegranskat)abstract
- Early-life inorganic arsenic exposure influences not only child health and development but also health in later life. The adverse effects of arsenic may be mediated by epigenetic mechanisms, as there are indications that arsenic causes altered DNA methylation of cancer-related genes. The objective was to assess effects of arsenic on genome-wide DNA methylation in newborns. We studied 127 mothers and cord blood of their infants. Arsenic exposure in early and late pregnancy was assessed by concentrations of arsenic metabolites in maternal urine, measured by high performance liquid chromatography-inductively coupled plasma mass spectrometry. Genome-wide 5-methylcytosine methylation in mononuclear cells from cord blood was analyzed by Infinium HumanMethylation450K BeadChip. Urinary arsenic in early gestation was associated with cord blood DNA methylation (Kolmogorov-Smirnov test, P-value<10-15), with more pronounced effects in boys than in girls. In boys, 372 (74%) of the 500 top CpG sites showed lower methylation with increasing arsenic exposure (r S -values>-0.62), but in girls only 207 (41%) showed inverse correlation (r S -values>-0.54). Three CpG sites in boys (cg15255455, cg13659051 and cg17646418), but none in girls, were significantly correlated with arsenic after adjustment for multiple comparisons. The associations between arsenic and DNA methylation were robust in multivariable-adjusted linear regression models. Much weaker associations were observed with arsenic exposure in late compared with early gestation. Pathway analysis showed overrepresentation of affected cancer-related genes in boys, but not in girls. In conclusion, early prenatal arsenic exposure appears to decrease DNA methylation in boys. Associations between early exposure and DNA methylation might reflect interference with de novo DNA methylation.
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| 4. |
- Broberg, K., et al.
(författare)
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Exposure to inorganic arsenic and gene expression in peripheral blood
- 2016
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Ingår i: Arsenic Research and Global Sustainability - Proceedings of the 6th International Congress on Arsenic in the Environment, AS 2016. - 9781138029415 ; , s. 448-449
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Konferensbidrag (refereegranskat)abstract
- Arsenic is an established carcinogen and a risk factor for several non-malignant diseases. Mechanisms of arsenic toxicity may include interference with gene expression. The impact of arsenic exposure on gene expression was evaluated in women (n = 80) living in the Puna of the northern Argentinian Andes with varying concentrations (10–1251 μg/L) of arsenic in drinking water. DirectHyb HumanHT-12 v4.0 was used for genome wide gene expression analysis. Robust linear regression model was used to each array to evaluate the relations between arsenic exposure, gene expression and with the influence of arsenic metabolism efficiency. Also, Ingenuity Pathway Analysis (IPA) was performed to look for relevant pathways, diseases, networks etc. associated with the genes. In the association between arsenic and gene expression, most of the genes were downregu-lated. Pathway analyses revealed different expression pattern associated with arsenic exposure between women with high and low urinary %MMA, indicating variation in arsenic susceptibility by arsenic-methylation.
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| 5. |
- Dahlén, A, et al.
(författare)
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Analysis of the distribution and frequency of trisomy 7 in vivo in synovia from patients with osteoarthritis and pigmented villonodular synovitis
- 2001
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Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 131:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- Osteoarthritis (OA) and pigmented villonodular synovitis (PVNS) are disorders associated with trisomy 7. The aim of the present study was to determine the frequency and distribution of the cells with +7 in vivo by analyzing sections of paraffin-embedded synovia from patients affected by OA, PVNS, other forms of synovitis [hemorragic synovitis (HS) and chronic synovitis (CS)], and from individuals without joint disease. Fluorescence in situ hybridization (FISH), using a centromeric probe for chromosome 7, showed that the mean frequency of trisomic nuclei in 5-microm sections was highest in PVNS (9.0%), followed by CS (5.9%), OA (5.6%), and HS (4.6%), whereas trisomic nuclei were rare (0.7%) in normal tissue. When 8-microm sections were studied, the frequencies of trisomic cells in OA and control synovia increased to 6.7% and 1.5%, respectively. Trisomic nuclei were found in all cases, including those for which cytogenetic analysis of short-term cultures had not disclosed any trisomic cells. Overall, the trisomic cells were scattered within the tissue. However, small clusters of cells with +7 were found in three cases. By hematoxylin-eosin staining of the slides used for FISH analysis it could be shown that the clustered trisomic cells were proliferating synoviocytes within villous extensions of the synovial membrane.
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| 6. |
- Lundh, Thomas, et al.
(författare)
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Cadmium and mercury exposure over time in Swedish children.
- 2016
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Ingår i: Environmental Research. - : Elsevier BV. - 1096-0953 .- 0013-9351. ; 150, s. 600-605
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Tidskriftsartikel (refereegranskat)abstract
- Knowledge about changes in exposure to toxic metals over time remains very sparse, in particular for children, the most vulnerable group. Here, we assessed whether a reduction in environmental pollution with cadmium (Cd) and mercury (Hg) caused a change in exposure over time. In total, 1257 children (age 4-9) in two towns in Sweden were sampled once in 1986-2013. Blood concentrations of Cd (b-Cd; n=1120) and Hg (b-Hg; n=560) were determined.
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| 7. |
- Wahlberg, K., et al.
(författare)
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Filaggrin variations are associated with PAH metabolites in urine and DNA alterations in blood
- 2019
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Ingår i: Environmental Research. - : Elsevier BV. - 0013-9351 .- 1096-0953. ; 177
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Tidskriftsartikel (refereegranskat)abstract
- Dermal chemical exposure is common in many professions. The filaggrin protein is important for the skin barrier and variations in the filaggrin gene (FLG) may influence the uptake of chemicals via the skin, and consequently, the degree of systemic effects. The aim of this study was to investigate, in chimney sweeps with occupational exposure to polycyclic aromatic hydrocarbons (PAH) from soot, the influence of variation in FLG on internal PAH dose and DNA alterations, including epigenetic, previously linked to cancer and cardiovascular disease. We used TaqMan PCR to genotype 151 chimney sweeps and 152 controls for four FLG null variants (R501X, R2447X, S3247X and 2282del4) which cause impaired skin barrier, and FLG copy number variation (12th repeat, CNV12) which potentially is beneficial for the skin barrier. The internal dose of PAH was represented by urinary PAH metabolites (e.g. 1-hydroxypyrene and 3-hydroxybenzo[a]pyrene) that we measured by LC-MS/MS. We measured epigenetic alterations (methylation of AHRR and F2RL3) in blood by pyrosequencing; and DNA alterations (telomere length and mitochondrial DNA copy number) by real-time PCR. Hypomethylation of AHRR or F2RL3 is a risk factor for lung cancer and shorter telomere length a risk factor for cardiovascular disease. The frequencies of FLG null were 8.6 and 11.8% (p = 0.35), and CNV12 27.8 and 19.7% (p = 0.09) in chimney sweeps and controls, respectively. We found that among chimney sweeps working predominately with soot sweeping (high PAH exposure), CNV12 carriers had lower concentrations of PAH metabolites in urine compared with non-carriers (median 1-hydroxypyrene = 0.37 vs 0.86 μg/g creatinine respectively; p = 0.025 by linear regression models adjusted for age, BMI and smoking) compared to sweeps not carrying CNV12. Further, FLG null was associated with approximately 2.5% higher methylation of F2RL3 (cg03636183, p = 0.019 after adjustment for exposure group, age, BMI and smoking). FLG null was associated with approximately 7% shorter telomere length (p = 0.015, adjusted model). Our results suggest that FLG variations may influence the dose of PAH in highly exposed workers, possibly via dermal uptake. It also suggests that FLG variation may influence the degree of (epi)genotoxicity in the body. FLG variation is common in the working population and should be considered in risk assessment. © 2019
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