ABSTRACT
Lipid peroxidation of biological membranes in cells and tissues results in the formation of toxic aldehydes that are causally involved in some of the pathophysiological effects associated with oxidative stress (1). Among the many different aldehydes generated during lipid pero xidation, 4-hydroxy-2-nonenal (HNE) is one of the major products and has been shown to have a number of adverse biological effects (2). It is known that HNE is a substrate of glutathione S-transferases (GSTs) (3,4), a family of enzymes that catalyzes the conjugation of reactive chemicals with glutathione and plays an important role in protecting cells. In mammalian species, GSTs have been divided into four classes, based on their primary structure (5): α, μ, π, and Θ. It has been estab lished that the π-class GST-P (homodimer of GST-Yp subunit), which is hardly detectable in normal rat liver, becomes constitutively expressed in hyperplastic nodules and hepatocellular carcinomas (4,6). The high incidence of derepression of GST-P gene expression in the preneoplastic lesions and hyperplastic nodules has suggested that the mechanisms regulating the expression of this gene may be closely related to the neo plastic transformation of the rat liver. It has been reported that over-
expression of GSTs is related to an increase in resistance to anticancer drugs or alkylating agents (7-11). In addition, it is known that the ras oncogene, which is most commonly involved in human tumors, trans forms rat liver epitherial cells, demonstrating a multidrug-resistant phe notype along with increased GST-P gene expression (12-14).
