Effect of sulfur exposure on protease activity in human peripheral blood lymphocytes.
Sulfur mustard is a chemical warfare blistering agent for which neither the mechanism of action nor an antidote is known. Papirmeister et al. (1985) have postulated a biochemical hypothesis for mustard-induced cutaneous injury involving a sequelae of DNA alkylation, metabolic disruption and activation of protease. Human peripheral blood lymphocytes in cell cultures were employed as an in vitro model for alkylating agent toxicity. A chromogenic peptide substrate assay was used for detection of protease in lymphocytes treated with sulfur mustard or chloroethyl ethyl sulfide. Exposure of human peripheral blood lymphocytes from normal donors to these alkylating agents resulted in an increase in cell associated protease activity. This increase in protease activity may contribute to the pathology or act as an indicator to predict methods of therapeutic intervention for sulfur mustard toxicity.
Biochemical Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland 21010-5425.
F M
FM
Cowan
C A
CA
Broomfield
W J
WJ
Smith
D000477:Alkylating Agents; D004249:DNA Damage; D010450:Endopeptidases / Q000378:metabolism*; D006801:Humans; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology; D009151:Mustard Gas / Q000633:toxicity*; D011480:Protease Inhibitors / Q000494:pharmacology; D013379:Substrate Specificity
D000477:Alkylating Agents; D011480:Protease Inhibitors; D010450:Endopeptidases; D009151:Mustard Gas