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Multiomic analysis of Lewisite exposed human dermal equivalent tissues.

Elizabeth S Dhummakupt1, Conor C Jenkins1, Gabrielle M Rizzo1

  • 1U.S. Army, Combat Capabilities Development Command (DEVCOM) Chemical Biological Center, Aberdeen Proving Ground, MD, 21010, USA.

Chemico-Biological Interactions
|November 1, 2024
PubMed
Summary

Lewisite, a chemical warfare agent (CWA), poses a significant threat due to existing stockpiles. This study investigated Lewisite's effects on human skin tissues, revealing its cellular and histological impacts through multiomic analysis.

Keywords:
Chemical warfare agentInflammationMetabolitesProteinsS100Vesicant

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Area of Science:

  • Toxicology
  • Chemical Warfare Agents
  • Dermatology

Background:

  • Lewisite (L) is an arsenical vesicant chemical warfare agent (CWA) developed during WWI.
  • Despite no documented use in warfare, significant global stockpiles remain.
  • The potential for illicit production and existing stockpiles constitute a serious threat.

Purpose of the Study:

  • To investigate the toxicological effects of Lewisite on human dermal equivalent tissues.
  • To evaluate cellular viability, histological changes, and multiomic responses to Lewisite exposure.

Main Methods:

  • Exposure of human dermal equivalent tissues (EpiDerm™/EpiDerm™-FT) to Lewisite.
  • Assessment of cellular viability using standard assays.
  • Histological examination of tissue damage.
  • Comprehensive multiomic analysis to understand molecular-level responses.

Main Results:

  • Lewisite exposure significantly impacted cellular viability in human dermal equivalent tissues.
  • Histological analysis revealed characteristic tissue damage consistent with vesicant exposure.
  • Multiomic analysis identified specific molecular pathways affected by Lewisite, providing insights into its mechanism of action.

Conclusions:

  • Lewisite causes significant damage to human dermal equivalent tissues at cellular and histological levels.
  • Multiomic analysis provides a deeper understanding of Lewisite's toxicological mechanisms.
  • These findings highlight the continued threat posed by Lewisite and inform risk assessment and medical countermeasures.