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Activation of alpha-human tumour necrosis factor (TNF-) by human monocytes (THP-1) exposed to 2-chloroethyl ethyl sulphide (H-MG)

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland USA

Robert L Von Tersch

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland USA

Clarence A Broomfield

US Army Medical Research Institute of Chemical Defense, Aberdeen Proving Ground, Maryland USA

Tumour necrosis factor (TNF) is a monokine produced by monocytes and macrophages in response to different stim uli. To determine whether vesicant agents such as half- mustard gas (H-MG; chemical structure: ClCH₂CH ₂SCH₂CH₃) may induce the release of TNF- in human monocytes (THP-1), ELISA experiments were con ducted at different post exposure times. The results indi cate that: (1) Significant increases in the TNF- (pg mL^-1) concentration were observed as a function of time when THP-1 cells were exposed to 100 µL of 2 M H-MG. A spe cific serine-type protease inhibitor, N-p-tosyl-L-lysine chloromethyl ketone (TLCK), led to partial but significant inhibition of TNF activation. (2) Furthermore, this labora tory detected the generation of spin adducts of 2-methyl-2- nitrosopropane (MNP) having a resemblance to MNP adducts generated from hydrogen atom abstraction of pro tein constituents.¹ The EPR/Spin Trapping data indicate the trapping of by-products of protein degradation after exposure to H-MG. TNF- may play a role as a biochemi cal marker for pathophysiological changes induced by H- MG or related agents.

Key Words: TNF- • human monocyte • THP-1 • ELISA • EPR/Spin trapping • MNP • protein degradation • half-mus tard gas • vesicant agent

Human & Experimental Toxicology, Vol. 14, No. 7, 547-553 (1995)
DOI: 10.1177/096032719501400701


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