Cystathionine pathway-dependent cytotoxicities of diethyl maleate and diamide in rat and human hepatoma-derived cell cultures.

Abstract	Glutathione (GSH) plays a role in many toxicologically important metabolic processes. It was previously established that L-buthionine S,R-sulphoximine (BSO), a specific inhibitor of (- glutamylcysteine synthetase, reduces the GSH content more efficiently in rat (Fa32) than in human (HEp-G2) hepatoma-derived cells. We therefore investigated whether the cystathionase inhibitor propargylglycine (PPG) could further decrease the BSO-induced GSH depletion in HEp-G2 cells. The influence of the cystathionine precursors N-acetylmethionine, methionine and homocysteine on the cytotoxicity of diethyl maleate (DEM) and diamide [1,1'-azobis(N,N-dimethylformamide)] was also investigated. PPG reduced the GSH content in both cell lines. A further GSH decrease in HEp-G2 was obtained when using a BSO + PPG combination containing relatively high concentrations of PPG. BSO diminished the toxicity of PPG. Homocysteine was the most efficacious of the tested cystathionine precursors in increasing the GSH content and reducing the cytotoxicity of DEM and diamide in Fa32 and HEp-G2 cells.
Authors	Paul J Dierickx, Jacques O De Beer, Ellen M Scheers
Journal	Alternatives to laboratory animals : ATLA (Altern Lab Anim) 2002 Jan-Feb Vol. 30 Issue 1 Pg. 61-8 ISSN: 0261-1929 [Print] England
PMID	11827570 (Publication Type: Journal Article)
Chemical References	Alkynes Enzyme Inhibitors Maleates Homocysteine Diamide Cystathionine Buthionine Sulfoximine propargylglycine N-acetylmethionine Methionine Cystathionine gamma-Lyase diethyl maleate Glutathione Glycine
Topics	Alkynes (pharmacology) Animals Buthionine Sulfoximine (pharmacology) Carcinoma, Hepatocellular (pathology) Cell Death (drug effects) Cystathionine (metabolism) Cystathionine gamma-Lyase (antagonists & inhibitors) Diamide (toxicity) Enzyme Inhibitors (pharmacology) Glutathione (metabolism) Glycine (analogs & derivatives, pharmacology) Homocysteine (pharmacology) Humans Liver Neoplasms (pathology) Liver Neoplasms, Experimental Maleates (toxicity) Methionine (analogs & derivatives, pharmacology) Rats Tumor Cells, Cultured

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