Common non-epigenetic drugs as epigenetic modulators

•Drugs can interfere with DNA methylation and histone modifications.•Mechanisms involve covalent binding, interaction with DNA repair, and via pathway branches.•Epigenetic effects seem frequent involving up to 5% of all drugs.•Pleiotropic epigenetic effects of non-epigenetic drugs may become a drug test requirement.

Epigenetic effects are exerted by a variety of factors and evidence increases that common drugs such as opioids, cannabinoids, valproic acid, or cytostatics may induce alterations in DNA methylation patterns or histone conformations. These effects occur via chemical structural interactions with epigenetic enzymes, through interactions with DNA repair mechanisms. Computational predictions indicate that one-twentieth of all drugs might potentially interact with human histone deacetylase, which was prospectively experimentally verified for the compound with the highest predicted interaction probability. These epigenetic effects add to wanted and unwanted drug effects, contributing to mechanisms of drug resistance or disease-related and unrelated phenotypes. Because epigenetic changes might be transmitted to offspring, the need for reliable and cost-effective epigenetic screening tools becomes acute.