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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)
Carmen M Arroyo
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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[Abstract]
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