Epigenetics in toxicology: the implications of epigenetic alterations driven by external exposures for human health

The prospect that non-genotoxic environmental exposures of physical, chemical or social nature act on epigenetic mechanisms opens a new emerging field in toxicology. Epigenetics refers to the stable changes in gene expression programming that could alter the phenotype in absence of a change in DNA sequence. Epigenetic modifications, which include amongst others DNA methylation, covalent modifications of histone tails, and regulation by non-coding RNAs, play a significant role in normal development and genome stability and constitute a mechanism of genome adaptation to external stimuli. However, the process of adaptation may bring about adverse effects resulting in the development of pathologies. Exogenous agents could therefore have long-term toxicity without changing the DNA sequence that lasts well after the initial insult is gone. Such toxicities go undetected by current screening methods. An increasing number of chemicals referred to as epimutagens is emerging. The current challenge in toxicology is to develop screening methods that would detect epigenetic alterations caused by diverse environmental agents.

Trefwoorden:epigenetics, toxicology, risk assessment, 3R alternative methods