Pseudo-Epidermis: A Model System for Investigating Molecular and Cellular Pathways of Cutaneous Epidermal Toxicity from Sulfur Mustard
Abstract
Damage to DNA, Inhibition of DNA replication and mitosis, appearance of abnormal keratin peptide and large differentiated cells and, finally, death of cells occur dose- and time-responsively in submerged cultures of keratinocytes exposed to bis-(b-chloroethyl)sulfide (BCES). However, the relevance of these Parameters to vesication in human skin exposed to mustard in vivo has yet to be established. The pseudo-epidermis cultured from human cutaneous keratinocytes offers a system in which the pathogenic importance of each of these parameters can be evaluated. To establish the validity of the system, it is necessary to show that the pseudo-epidermis undergoes similar dose- and time-dependent cytotoxicity from BCES as is observed in the human skin after topical exposure to the mustard. This report includes data which demonstrate a dose- and time-dependent destruction of the germinative layer in human pseudo-epidermis after topical application of BCES. In addition, data are included to show that DNA is a primary target for BCES in pseudo-epidermis as it is in vivo. Also included in this report is a proposed sequence of molecular and cellular events to account for cytotoxicity in the germinative population of the pseudo-epidermis after exposure to BCES.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 13, 1993
- Accession Number
- ADP008762
Entities
People
- F. L. Vaughan
- I. A. Bernstein
- L. I. Bernstam
- P. P. Lin
- Y. H. Yang
Organizations
- University of Michigan