ABSTRACT
Cellular exposure to antioxidants, xenobiotics, and drugs results in altered expres sion of genes encoding transcription factors that regulate the expression of drugmetabolizing enzymes. Cytochromes P450, P450 reductase, and other one-electron reducing enzymes metabolically activate xenobiotics and drugs to generate elec trophiles and reactive oxygen species, resulting in electrophilic and oxidative stress leading to neoplasia (1). The detoxifying or chemopreventive enzymes, on the other hand, provide protection to the cells either by competing with the activating enzymes and preventing the formation of electrophiles and reactive oxygen species or by cat alyzing their detoxification from the cells (2-6). The detoxifying enzymes include NAD(P)H:quinone oxidoreductases (NQOj and N Q 02), which catalyze two-electron reduction and detoxification of quinones (2-6); glutathione S-transferases (GSTs), which conjugate hydrophobic electrophiles and reactive oxygen species with glu tathione (7-9); UDP-glucuronosyl-transferases (UDP-GT), which catalyze the conju gation of glucuronic acid with xenobiotics and drugs (10); epoxide hydrolase, which inactivates epoxides (11); y-glutamylcysteine synthetase (y-GCS), which plays a key role in the regulation of glutathione metabolism (12); and so on. The induc tion of detoxifying enzymes is one mechanism of critical importance in achieving chemoprevention.
