ABSTRACT
Glutathione is ubiquitous and the most abundant intracellular thiol-containing compound which serves a variety of functions in cells. It reacts with a wide spectrum of foreign substances to form glutathione conjugates which in turn are converted to the N-acetylcysteine derivative (mercapturic acid) by removal of the glutamyl moiety, cysteine moiety, and N-acetylation of cysteine conjugate. The formation of glutathione conjugate is facilitated by glutathione transferases 1 (GST: EC.2.1.5.18), a major group of versatile proteins that are involved in the cellular detoxication of an extensive variety of electrophilic chemicals. Among their other activities, they catalyze the conjugation of a wide number of electrophilic substances to GSH, 1 bind both covalently and noncovalently to various xenobiotics as well as to endogenous metabolites 2 and express selenium-independent glutathione peroxidase activity. 3 As the ultimate reactive carcinogenic forms of chemical carcinogens are associated with electrophilic substances and organic hydroperoxides, the GST (which inactivates them) has to be considered anticarcinogenic. Robertson et al. 4 reported that the three major classes of human liver cytosolic GST are very efficient in the conjugation of GSH to the diol oxide 7β, 8a-dihydroxy-9a,10a-oxy-7,8,9,10-tetrahydrobenzo(a)pyrene and in particular to ( + )-enantiomer which has been shown to be the most carcinogenic intermediate of polycyclic aromatic hydrocarbons. The GSTs purified from human lung 5 and liver 6 cytosols are also able to catalyze the conjugation of other benzo(a)pyrene epoxides with GSH. On the other hand, the presence of substantial initial GST activity or the development of elevated levels of GST activity, as well as the presence of particular isoenzymes in tumor cells, could protect them against the killing effect of anticancer drugs by conjugation of these compounds to GSH. An extensive body of information on the role that GSTs have in detoxifying xenobiotics, as well as on their structural, kinetic, and immunological characteristics, can be obtained by consulting the excellent reviews 7 , 17 that have accumulated since 1961 when they were identified as GSTs. 1 The printed proceedings of the international meeting held in Dublin in 1986 is also an available source of information to understand the importance of GSTs in carcinogenesis. 18 The scope of this article is limited only to the studies dealing with their presence and possible significance in human tumor tissues and human tumor cell lines.
