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Human & Experimental Toxicology
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Cysteine Conjugate Toxicity in a Human Cell Line: Correlation with C-S Lyase Activity in Human Hepatic Tissue

Lorraine D. Buckberry

Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK

Ian S. Blagbrough

Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK

P. Nicholas Shaw

Department of Pharmaceutical Sciences, University of Nottingham, Nottingham NG7 2RD, UK

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.

Human & Experimental Toxicology, Vol. 12, No. 4, 329-335 (1993)
DOI: 10.1177/096032719301200412
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