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Sulfur mustard-induced epigenetic modifications over time - a pilot study.

Thilo Simons1, Dirk Steinritz2, Birgit Bölck3

  • 1Bundeswehr Institute of Pharmacology and Toxicology, 80937, Munich, Germany.

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Sulfur mustard (SM) exposure can lead to lasting health issues. This study reveals SM causes persistent epigenetic changes, specifically DNA methylation, in cells and skin samples long after exposure.

Keywords:
5-methylcytosineDNA methylationEarly endothelial cellsHistone modificationLong-term health effects

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Area of Science:

  • Toxicology
  • Molecular Biology
  • Epigenetics

Background:

  • Sulfur mustard (SM) is a chemical warfare agent known to cause long-term health effects.
  • The exact mechanisms behind these chronic effects are not fully understood, but epigenetic alterations are a potential explanation.
  • Epigenetics involves changes in gene function without altering the DNA sequence, primarily through DNA methylation and histone modifications.

Purpose of the Study:

  • To investigate the long-term effects of sulfur mustard (SM) on DNA methylation and histone modifications.
  • To compare in vitro findings in early endothelial cells (EEC) with in vivo data from a human skin sample exposed to SM approximately one year prior.

Main Methods:

  • Early endothelial cells (EEC) were exposed to low concentrations of SM (0.5 and 1.0μM).
  • DNA methylation and specific histone modifications (acetylation and di-methylation) were analyzed 24 hours post-exposure and after 2-4 cell passages.
  • A human skin sample from an individual with a history of accidental SM exposure was analyzed in parallel.

Main Results:

  • Sulfur mustard (SM) exposure induced only minor alterations in histone modifications.
  • A significant and notable increase in DNA methylation was observed in EEC after multiple cell passages.
  • The human skin sample also exhibited elevated DNA methylation, consistent with the in vitro findings.

Conclusions:

  • Sulfur mustard (SM) exposure causes epigenetic modifications, specifically increased DNA methylation.
  • These SM-induced epigenetic changes appear to be persistent over time.
  • The findings suggest that epigenetic alterations may underlie the long-term health consequences of sulfur mustard exposure.