Accession Number:

ADA440959

Title:

Dimethyl Sulfoxide Accelerates Mustard Gas-Induced Skin Pathology Journal of Medical Chemical, Biological and Radiological Defense

Descriptive Note:

Journal article

Corporate Author:

ARMY MEDICAL RESEARCH INST OF CHEMICAL DEFENSE ABERDEEN PROVING GROUND MD DEPT OF PHARMACY

Report Date:

2005-01-01

Pagination or Media Count:

8.0

Abstract:

Dimethyl sulfoxide DMSO, when used as a percutaneous carrier or as a required solvent for drugs, may have modulating effects on drug mechanisms and untoward effects on subject tissues. In this collaborative study, anhydrous DMSO was used as a vehicle for peptide caspase inhibitors of sulfur mustard gas HD-induced apoptosis in hairless guinea pig skin. Results of the inhibition study are the subject of a companion report. In this present manuscript we describe the observed morphological effects of DMSO on hairless guinea pig skin when used as a drug vehicle and as pretreatment to HD exposure. DMSO was applied topically to skin sites as a vehicle control 30 minutes prior to neat HD-vapor exposure 7-8 minutes. Unexposed skin sites also treated for 30 minutes with DMSO were used as controls. Selected exposed and unexposed skin sites, harvested at 6 hours and 24 hours postexposure, were either paraffin-processed for routine histopathology or epoxy embedded for ultrastructural pathology. HD-exposed skin sites pretreated with DMSO presented a marked acceleration and exacerbation of characteristic HD-induced pathologies. At six hours postexposure, epidermal basal cells presented pyknotic nuclear and degenerative cytopathologies usually not seen until later times. Also at this same time, microvesicles in the basement membrane zone, usually not in evidence until 10-12 hours postexposure, were a persistent feature of the pathology. At 24 hours postexposure, cleavages of the dermalepidermal junction were more expansive than with typical HD exposure. In addition, unexposed control sites treated with DMSO but not with HD presented an exaggerated inflammatory response of the papillary dermis. The inflammation-primed dermis induced by DMSO may be largely responsible for the acceleration and exacerbation of the characteristic HD-induced skin pathology observed in this study.

Subject Categories:

  • Medicine and Medical Research
  • Organic Chemistry
  • Physical Chemistry

Distribution Statement:

APPROVED FOR PUBLIC RELEASE