In vitro methods for the assessment of L-cysteine conjugate toxicity

By Buckberry, L.D. - Adcock, H.J. - Adler, J. - Blagbrough, I.S. - Gaskin, P.J. - Shaw, P.N.

L-Cysteine conjugates are normally metabolised via N-acetylation to produce a mercapturic acid. However, a recently identified metabolic route (C-S lysis) may lead to the generation of an unstable thiol which has been demonstrated to be responsible for toxicity in various mammalian species. Human Chang liver cells were challenged with a number of established L-cysteine conjugates. The cellular toxicity of these compounds was determined using a range of assay procedures, which provided differing information, depending on the assay method used. These observations were then investigated in order to establish which system would provide the most reliable indication of C-S lyase toxicity and whether any information on the mechanism of action could be obtained by these assay methods.