Journal
EPIGENOMICS
Volume 8, Issue 2, Pages 167-179Publisher
FUTURE MEDICINE LTD
DOI: 10.2217/epi.15.78
Keywords
epigenetic drug effects; Gaussian mixture modeling; human DNA; opioids; pharmacoepigenomics
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Funding
- Else Kroner-Fresenius Foundation (EKFS)
- Research Training Group Translational Research Innovation - Pharma (TRIP)
- Landesoffensive zur Entwicklung wissenschaftlich-okonomischer Exzellenz (LOEWE)
- LOEWE-Zentrum fur Translationale Medizin und Pharmakologie
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Background: Increased global DNA methylation in the blood of patients chronically exposed to opioids had been interpreted as an indication of an epigenetic action of this drug class. Materials & methods: To strengthen the causality, human MCF7 cells were cultured in media with the addition of several known or potential modulators of DNA methylation including methadone. Results: Following 3 days of incubation with several different known or potential epigenetic modulators, global DNA methylation, quantified at LINE-1 CpG islands, showed a large variability across all treatments ranging from 27.8 to 63%. Based on distribution analysis of the global methylation of human DNA exposed to various potential modulators, present in vitro experiments showed that treatment with the opioid methadone was associated with an increased probability of hypermethylation. Conclusion: This strengthens the evidence that opioids interfere with mechanisms of classical epigenetics.
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