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DNA methylation modifications in human mesenchymal stem cells  induced by exposure to endocrine disrupting plasticiser metabolites MBP, MEP, MBzP, MEHP and MINCH
Uppsala University, Disciplinary Domain of Science and Technology, Biology, Department of Organismal Biology, Environmental toxicology. Uppsala University, Disciplinary Domain of Science and Technology, Biology, Biology Education Centre. (EpiTox)
2022 (English)Independent thesis Advanced level (degree of Master (Two Years)), 80 credits / 120 HE creditsStudent thesis
Abstract [en]

Endocrine disrupting chemicals (EDCs) are exogenous substances which can modify the function of the endocrine system and lead to adverse health effects. Humans experience daily uncontrolled exposure to EDC mixtures. Predicting mixture effects is complicated since the chemicals may produce different effects when combined together. EDCs may produce epigenetic effects such as alterations of the DNA methylation, which could modify the expression of the gene. Previously, 14 chemicals linked to metabolism (mixture G1) were reported to induce DNA methylation changes in an in vitro model. Mixture G1 were based on a Swedish longitudinal study which had identified the chemical burden of >2300 pregnant women. This project aimed to study single chemical driver effects of five individual chemicals from mixture G1, namely the four phthalate metabolites monobutyl phthalate (MBP), monoethyl phthalate (MEP), monobenzyl pthtalate (MBzP), mono-(2-ethylhexyl) phthalate (MEHP) and the non-phthalate plasticiser Bis(7-methyloctyl) Cyclohexane-1,2-dicarboxylate (DINCH) metabolite 2-4-methyl-7-oxyoctyl-oxycarbonyl-cyclohexane carboxylic acid (MINCH). Human mesenchymal stem cells (hMSCs) were exposed to the five compounds individually at the same concentrations as in mixture G1. After exposure, DNA methylation changes in four CpG sites within PGM1, MYOF and HCFC1 genes were analysed. While som chemicals did not show statistically significant effects, one chemical showed significant effects and thus could be a potential driver. The discrepancy between the observed DNA methylation alterations in the analysed genes and the alterations in mixture G1 highlights the need for comparing mixture to single chemical effects to identify drivers within mixes and for increased understanding of mixture effects.

Place, publisher, year, edition, pages
2022. , p. 23
Keywords [en]
mixture effects, endocrine disrupting chemicals, EDC, phthalates, MBP, MBzP, MEP, MEHP, MINCH, plasticisers, metabolism
National Category
Genetics Cell Biology Biochemistry and Molecular Biology Developmental Biology
Identifiers
URN: urn:nbn:se:uu:diva-491310OAI: oai:DiVA.org:uu-491310DiVA, id: diva2:1721788
Subject / course
Toxicology
Educational program
Master Programme in Biology
Presentation
2022-12-05, 07.00009 Lärosal, EBC Hus 7, Norbyvägen 16, 752 36 Uppsala, 14:32 (English)
Supervisors
Examiners
Available from: 2023-03-10 Created: 2022-12-22 Last updated: 2023-03-10Bibliographically approved

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The full text will be freely available from 2026-01-01 15:14
Available from 2026-01-01 15:14

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CiteExportLink to record
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