Accession Number : AD0722733

Title :   Extracellular or Cell Membrane Toxic Reactions of Some Sulfur and Nitrogen Mustards.

Descriptive Note : Technical rept. Aug 66-Nov 70,

Corporate Author : EDGEWOOD ARSENAL MD

Personal Author(s) : Williamson,Charles E. ; Witten,Benjamin

Report Date : MAR 1971

Pagination or Media Count : 16

Abstract : Interpretation of experiments with short-lived sulfur and nitrogen mustards indicates that the toxic effects of these agents arise from extracellular or cell surface reactions rather than from exclusive alkylation of intranuclear deoxyribonucleic acid (DNA). Intravenous pretreatment of animals with sodium thiosulfate was observed to prevent the toxic effects of N, N'-ethylene-bis(5-(2-bromoethylthio) valeramide), (compound I, half life = approximately 4 seconds), but the pretreatment was not effective with N, N'-ethylene-bis-((2-chloroethylylthio)acetamide) (compound II, half life = 15 minutes). This suggests that only compound II exists sufficiently long after iv injection to pass from the thiosulfate-rich extracellular water into the thiosulfate-free intracellular compartment where it can produce toxic alkylations. The observation that compound I is toxic in the absence of thiosulfate suggests that its toxic alkylations are produced in the extracellular compartment. A common target could be the plasma membranes. N, N'-bis-(2-chloroethyl)-N-methylamine (HN2) was observed to pass from the extracellular water more rapidly than does its charged form N-2-chloroethyl-N-methylaziridinium chloride (compound III). Compound III is more toxic than HN2 and is most susceptible to thiosulfate pretreatment. These observations also suggest the cell plasma membranes as a possible site of the toxic reaction. (Author)


Subject Categories : Toxicology

Distribution Statement : APPROVED FOR PUBLIC RELEASE