A new paradigm in toxicology and teratology: altering gene activity in the absence of DNA sequence variation

Reprod Toxicol. 2007 Jul;24(1):20-30. doi: 10.1016/j.reprotox.2007.05.002. Epub 2007 May 22.

Abstract

'Epigenetics' is a heritable phenomenon without change in primary DNA sequence. In recent years, this field has attracted much attention as more epigenetic controls of gene activities are being discovered. Such epigenetic controls ensue from an interplay of DNA methylation, histone modifications, and RNA-mediated pathways from non-coding RNAs, notably silencing RNA (siRNA) and microRNA (miRNA). Although epigenetic regulation is inherent to normal development and differentiation, this can be misdirected leading to a number of diseases including cancer. All the same, many of the processes can be reversed offering a hope for epigenetic therapies such as inhibitors of enzymes controlling epigenetic modifications, specifically DNA methyltransferases, histone deacetylases, and RNAi therapeutics. 'In utero' or early life exposures to dietary and environmental exposures can have a profound effect on our epigenetic code, the so-called 'epigenome', resulting in birth defects and diseases developed later in life. Indeed, examples are accumulating in which environmental exposures can be attributed to epigenetic causes, an encouraging edge towards greater understanding of the contribution of epigenetic influences of environmental exposures. Routine analysis of epigenetic modifications as part of the mechanisms of action of environmental contaminants is in order. There is, however, an explosion of research in the field of epigenetics and to keep abreast of these developments could be a challenge. In this paper, we provide an overview of epigenetic mechanisms focusing on recent reviews and studies to serve as an entry point into the realm of 'environmental epigenetics'.

Publication types

  • Review

MeSH terms

  • Abnormalities, Drug-Induced / genetics*
  • Abnormalities, Drug-Induced / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • DNA Methylation
  • Environmental Pollutants / toxicity
  • Epigenesis, Genetic* / drug effects
  • Gene Expression Regulation, Developmental* / drug effects
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Genomic Imprinting
  • Histones / metabolism
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • RNA Interference
  • Teratology / trends*
  • Toxicology / trends*
  • X Chromosome Inactivation

Substances

  • Antineoplastic Agents
  • Environmental Pollutants
  • Histones