title: Cysteine conjugate toxicity in a human cell line: correlation with C-S lyase activity in human hepatic tissue.
abstract: C-S lyase enzymes catalyse the generation of mutagenic and/or cytotoxic thiols from cysteine conjugated xenobiotics. These cysteine conjugates are produced subsequent to glutathione conjugations as a metabolic step in the mercapturic acid pathway, traditionally thought of as a pathway solely associated with detoxification. Human Chang liver (HCL) cells were challenged with a range of cysteine conjugates demonstrated to be substrates for human hepatic C-S lyases. The cellular toxicity of these compounds was determined and it was observed that the rank order of substrate toxicity obtained for the HCL cells followed the rank order of C-S lyase activity of the substrates in a freshly isolated mitochondrial fraction of human tissue. The presence of C-S lyase activity was also established in this cell line.
authors.affiliation: Department of Pharmaceutical Sciences, University of Nottingham, UK.
authors.forename: L D
authors.initials: LD
authors.lastname: Buckberry
authors.forename: I S
authors.initials: IS
authors.lastname: Blagbrough
authors.forename: P N
authors.initials: PN
authors.lastname: Shaw
mesh_terms: D013437:Carbon-Sulfur Lyases; D002470:Cell Survival / Q000187:drug effects; D003545:Cysteine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D006801:Humans; D008190:Lyases / Q000378:metabolism*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology*; D014407:Tumor Cells, Cultured; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*
chemical_list: D015262:Xenobiotics; D008190:Lyases; D013437:Carbon-Sulfur Lyases; C019971:cysteine lyase; D003545:Cysteine