skip to main content

Title: Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect

Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMs), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysismore » to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor I, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors.« less
Authors:
 [1] ; ; ; ;  [2] ;  [3] ;  [4] ;  [2]
  1. Environmental and Occupational Health Sciences Institute (EOHSI), a Joint Institute of UMDNJ-RW Johnson Medical School and Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States), E-mail: gerecke@eohsi.rutgers.edu
  2. Environmental and Occupational Health Sciences Institute (EOHSI), Joint Institute of UMDNJ-RW Johnson Medical School and Rutgers University, 170 Frelinghuysen Road, Piscataway, NJ 08854 (United States)
  3. US FDA, National Center for Toxicological Research, Jefferson, AK (United States)
  4. Department of Biomedical Engineering, Rutgers, State University of New Jersey, Piscataway, NJ (United States)
Publication Date:
OSTI Identifier:
21182702
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 234; Journal Issue: 2; Other Information: DOI: 10.1016/j.taap.2008.09.020; PII: S0041-008X(08)00396-7; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ALKYLATING AGENTS; AUDITORY ORGANS; BIOPSY; BRASSICA; CHEMICAL WARFARE AGENTS; COMPUTER-AIDED MANUFACTURING; GENES; INFLAMMATION; MICE; POLYMERASE CHAIN REACTION; RECEPTORS; SKIN; SULFUR