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Diffuse Optical Spectroscopy for the Quantitative Assessment of Acute Ionizing Radiation Induced Skin Toxicity Using a Mouse Model
Published on: May 27, 2016
Toxicity of mustard gas skin lesions
1U.S. Army Medical Research Institute of Chemical Defense, Pathology Branch, Maryland 21010-5425, USA.
Abstract:
Although the exact pathogenesis of mustard gas-induced dermal toxicity remains elusive, morphopathological data gathered in controlled animal and in vitro investigations is providing important clues as to approximate mechanisms. Our laboratory has been studying dermal effects of the chemical warfare agent, sulfur mustard, in a variety of animal models, cultured isolated human cells, and in vitro organotypic skin models. Published anatomical, pathological, and ultrastructural results of these studies have documented consistent cellular and basement membrane zone effects irrespective of the model. Cellular effects include the early targeting of basal cells of the stratum basale to the exclusion of other epidermal cells, with nuclear and cytoplasmic indications of cell injury and cell death. Effects on the basement membrane zone include the formation of characteristic microvesicles in the lamina lucida of those models which possessed structural components of a true basement membrane. We are now investigating effects on proteins of the basement membrane microenvironment and correlate in the present paper the morphopathology of sulfur mustard dermal lesions with immunohistochemical study of bullous pemphigoid antigen, laminin, type IV collagen, and type VII collagen.
Insights
Sulfur mustard, a chemical warfare agent, causes dermal toxicity by damaging basal skin cells and the basement membrane. Research reveals consistent cellular injury and microvesicle formation, offering insights into its pathogenesis.
Area of Science:
- Dermatology
- Toxicology
- Cell Biology
Background:
- The exact pathogenesis of mustard gas-induced dermal toxicity is not fully understood.
- Morphopathological data from animal and in vitro studies offer clues to the mechanisms involved.
Purpose of the Study:
- To investigate the dermal effects of sulfur mustard (a chemical warfare agent) using various models.
- To correlate the morphopathology of sulfur mustard dermal lesions with specific proteins of the basement membrane microenvironment.
Main Methods:
- Utilizing a variety of animal models, cultured isolated human cells, and in vitro organotypic skin models.
- Conducting anatomical, pathological, and ultrastructural analyses.
- Performing immunohistochemical studies on bullous pemphigoid antigen, laminin, type IV collagen, and type VII collagen.
Main Results:
- Consistent cellular effects observed, including early targeting of basal cells in the stratum basale, showing signs of injury and cell death.
- Basement membrane zone effects include the formation of characteristic microvesicles in the lamina lucida.
- Investigating the impact on basement membrane microenvironment proteins.
Conclusions:
- Sulfur mustard causes significant dermal toxicity through specific cellular and basement membrane damage.
- The findings provide important insights into the mechanisms of sulfur mustard-induced skin lesions.
- Further investigation into basement membrane proteins is warranted.
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