Issue 4, 2018

Chromatin dynamics underlying latent responses to xenobiotics

Abstract

Pleiotropic xenobiotics can trigger dynamic alterations in mammalian chromatin structure and function but many of these are likely non-adverse and simply reflect short-term changes in DNA transactions underlying normal homeostatic, adaptive and protective cellular responses. However, it is plausible that a subset of xenobiotic-induced perturbations of somatic tissue or germline epigenomes result in delayed-onset and long-lasting adverse effects, in particular if they occur during critical stages of growth and development. These could include reprogramming, dedifferentiation, uncontrolled growth, and cumulative toxicity effects through molecular memory of prior xenobiotic exposures or altered susceptibility to subsequent xenobiotic exposures. Here we discuss the current evidence for epigenetic mechanisms underlying latent responses to xenobiotics, and the potential for identifying molecular epigenetic changes that are prodromal to overt morphologic or functional toxicity phenotypes.

Graphical abstract: Chromatin dynamics underlying latent responses to xenobiotics

Article information

Article type
Review Article
Submitted
28 Nov 2017
Accepted
26 Feb 2018
First published
28 Feb 2018

Toxicol. Res., 2018,7, 606-617

Spotlight

Advertisements