Chemical Blistering: Cellular and Macromolecular Components.
Rept. for 1 Jun 90-31 Dec 91,
MICHIGAN UNIV ANN ARBOR
Pagination or Media Count:
The mission of this project is to determine the cellular and molecular lesions associated with cutaneous vesication from bis2-chloroethylsulfide BCES. Cultures of keratinocytes are being used to focus on the direct interactions between the mustard and its cellular targets. The technical objectives include obtaining confirmation of the DNA as the primary molecular target of BCES in human epidermal keratinocytes, identifying and quantifying BCES-mediated adducts in DNA in relation to levels of exposure of cells to BCES, determining an explanation for the greater cytotoxicity of epidermal basal cells exposed to BCES as compared with differentiated cells, and elucidating the role of informational error in DNA in the cytopathogenic process. Progress to date includes determination of 21-22 min as the time for disappearance of half of the BCES in phosphate buffered saline at 370C in the absence of cells and about 8 min in their presence, confirmation that DNA synthesis is more sensitive to BCES than is protein or RNA synthesis in human keratinocytes, and demonstration that cytoxicity occurs in rat keratinocytes without dramatic decrease in cellular levels of nicotinamide adeninine dinucleotide. Mustard, Keratinocytes, Tissue Culture, Alkylation, Toxicity, Chemical Blistering, DNA Repair, DNA, Adducts, Humans, RAD V.
- Medicine and Medical Research