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Mechanisms of DNA-reactive and epigenetic chemical carcinogens: applications to carcinogenicity testing and risk

Tetyana Kobets1, Michael J Iatropoulos1, Gary M Williams1

  • 1Department of Pathology , New York Medical College , Valhalla , NY 10595 , USA . Email: Tetyana_Kobets@nymc.edu ; ; Tel: +1 914-594-3105.

Toxicology Research
|April 19, 2019
PubMed

Insights

This review distinguishes carcinogens based on their primary mechanism: direct DNA damage or epigenetic effects. Understanding these mechanisms is crucial for accurate carcinogenicity testing and human risk assessment.

Area of Science:

  • Toxicology
  • Molecular Biology
  • Cancer Research

Background:

  • Carcinogenic chemicals induce neoplasia via multiple pathways.
  • Mechanisms include direct interaction with nuclear DNA or indirect epigenetic effects.
  • Epigenetic effects involve alterations in regulatory macromolecules or cellular processes.

Purpose of the Study:

  • To detail the basis for distinguishing carcinogens by their primary mechanism of action.
  • To review DNA-reactive and epigenetic mechanisms of carcinogenesis.
  • To discuss applications in carcinogenicity testing and risk assessment.

Main Methods:

  • Review of scientific literature on chemical carcinogenesis mechanisms.
  • Analysis of DNA reactivity versus epigenetic activity in carcinogens.
  • Discussion of implications for regulatory science.

Main Results:

  • Carcinogens can be categorized by their primary mode of action: DNA reactivity or epigenetic influence.
  • Distinct molecular events characterize each carcinogenic pathway.
  • This distinction has significant implications for evaluating chemical safety.

Conclusions:

  • Differentiating between DNA-reactive and epigenetic carcinogens is essential.
  • This knowledge improves the accuracy of carcinogenicity testing protocols.
  • Understanding mechanisms enhances human health risk assessment for chemical exposures.

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