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Epigenetics and cancer: implications for drug discovery and safety assessment

Jonathan G Moggs1, Jay I Goodman, James E Trosko

  • 1Syngenta CTL, Alderley Park, Cheshire SK10 4TJ, UK.

Toxicology and Applied Pharmacology
|April 20, 2004
PubMed

Insights

Chemicals and drugs can impact human health by altering DNA and cellular growth. Epigenetic mechanisms, like DNA methylation and chromatin changes, also affect gene expression and toxicity, including cancer.

Area of Science:

  • Toxicology and Pharmacology
  • Epigenetics
  • Molecular Biology

Background:

  • Chemicals and drugs pose risks to human health, potentially causing cancer through DNA damage or altered cellular growth.
  • Gene expression changes, previously thought to be solely receptor-mediated, are now understood to be influenced by diverse epigenetic mechanisms.

Purpose of the Study:

  • To explore the interplay between genetic alterations and epigenetic modifications in regulating cell growth.
  • To discuss the implications of these interactions for drug discovery and safety assessment.

Main Methods:

  • Review of recent evidence on epigenetic mechanisms influencing gene expression and cellular behavior.
  • Focus on molecular events such as DNA methylation, chromatin modification, and cell surface molecule function.

Main Results:

  • Epigenetic mechanisms, including DNA methylation and chromatin alterations mediated by enzymes like DNA methyltransferases and histone modifiers, can establish and maintain altered epigenetic states.
  • These epigenetic changes can significantly alter gene expression, leading to permanent or reversible changes in cellular behavior.

Conclusions:

  • Epigenetic modifications play a crucial role in cellular behavior and toxicity, extending beyond traditional DNA damage pathways.
  • Understanding the interplay between genetic and epigenetic changes is vital for accurate drug safety assessment and the development of novel therapeutics.

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