Bioactivation Mechanism and Cytotoxicity of S(2-Chloro-1,1,2-Trifluoroethyl)-L-Cysteine
Glutathione conjugation of electrophilic xenobiotics is an important cellular detoxication mechanism. The nephrotoxicity and nephrocarcinogenicity of certain halogenated alkenes, however, may be attributed to glutathione S-conjugate formation followed by metabolism of the glutathione S-conjugates to the corresponding cysteine S-conjugates, which are metabolised by renal cysteine conjugate β-lyase (β-lyase) to ammonia, pyruvate and a thiol (Dekant et al., 1986a,b; Elfarra and Anders, 1984). The thiols thus formed are thought to lose hydrogen halide or tautomerise to yield reactive, electrophilic species (Anders et al., 1987; Dekant et al., 1986c) that may be the ultimate toxic metabolites. The chemical nature of these metabolites formed from cysteine S-conjugates has, however, not been characterized.
KeywordsSulphide Glutathione Bromide Fluoride Cysteine
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- Dekant, W., Lash, L.H., and Anders, M.W., 1987, Prog. Natl. Acad. Sci. U.S.A., in press.Google Scholar