Methadone induces hypermethylation of human DNA.
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.


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.


CONCLUSIONS
This strengthens the evidence that opioids interfere with mechanisms of classical epigenetics.
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Claudia
C
Knothe
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
Alexandra
A
Doehring
DataBionics Research Group, University of Marburg, Hans-Meerwein-Straße, 35032 Marburg, Germany.
Alfred
A
Ultsch
Institute of Clinical Pharmacology, Goethe - University, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.|Fraunhofer Institute for Molecular Biology & Applied Ecology IME, Project Group Translational Medicine & Pharmacology TMP, Theodor-Stern-Kai 7, 60596 Frankfurt am Main, Germany.
Jörn
J
Lötsch
D000701:Analgesics, Opioid / Q000494:pharmacology*; D019175:DNA Methylation / Q000187:drug effects*; D044127:Epigenesis, Genetic / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D020084:Long Interspersed Nucleotide Elements / Q000187:drug effects / Q000235:genetics; D061986:MCF-7 Cells; D008691:Methadone / Q000494:pharmacology*; D017422:Sequence Analysis, DNA
D000701:Analgesics, Opioid; D008691:Methadone
Gaussian mixture modeling; epigenetic drug effects; human DNA; opioids; pharmacoepigenomics