Role of Glutathione and N-Acetylcysteine as Inhibitors of Mutagenesis and Carcinogenesis

Cysteine and glutathione are involved in the synthesis of many pigments, this process being mediated by cysteinyldopas or glutathionedopas. Although cysteine is the focal compound of organic thiol metabolism, glutathione, a tripeptide, is the most ubiquitous aminothiol. Glutathione reacts with many endogenous metabolites and with exogenously originated electrophilic compounds, forming reduced glutathione (GSH) conjugates. In fact, since GSH combines with reactive electrophilic metabolites of xenobiotics and, hence, protects nucleophilic cell compounds, toxic effects are exerted only after a net depletion of intracellular GSH stores. The effects of N-acetylcysteine and GSH in liver carcinogenesis were investigated by the use of an experimental model in the rat, involving a discontinuous cyclic dietary regimen containing the aromatic amine 2-acetylaminofluorene. Multiple mechanisms are involved in the inhibitory effects of thiols in mutagenesis and carcinogenesis. All the known inhibitors of mutagenesis and carcinogenesis seem to share the dual role of inhibitors and of stimulators, depending on the situation.