ABSTRACT
ACTH, adrenocorticotropic hormone; BCNU, l,3-bis-(2-chloroethyl)-lnitrosourea; BHA, 2(3)-te;t-butyl-4-hydroxyanisole; ( + )-anti-BPDE, ( + )- *mfr-benzo[tf]pyrene-7,8-diol 9,10-epoxide; CDNB, l-chloro-2,4-dinitro benzene; DEB, 1,2,3,4-diepoxy butane; G-site, glutathione binding site; GST, glutathione transferase; HPLC, high performance liquid chromato graphy; HPV, human papilloma virus; H-site, hydrophobic substrate binding site; HSTF, heat-shock transcription factor; MGST1; microsomal glutathione transferase; NF-GMa, nuclear factor for granulocyte/macrophage colony-stimulating factor gene promoter a; PAH, polycyclic aromatic hydrocarbon; PAGE, polyacrylamide gel electrophoresis; PCR, polymerase chain reaction; RFLP, restriction fragment length poly morphism; SCE, sister chromatid exchange; SDS, sodium dodecyl sulfate
Introduction
Glutathione transferases (GSTs) function as detoxication enzymes and are generally considered to play a prominent role in cellular defense against electrophilic chemical species, of endogenous as well as xenobiotic origins. It is reasonable to assume that variabilities in the expression of these detoxication enzymes in humans would alter the biotransformation of many carcinogens and other noxious agents that may serve as etiological factors in degenerative processes. The absence of specific isoenzymes affects the tolerance of the organism to chemical challenges and may result in an increased rate of somatic mutations and higher susceptibility to disease. The following chapter describes the multiplicity of GSTs, the variability in their expression, and known genetic polymorphisms in humans. The impact on detoxication at the levels of enzymes, cells, and the organism, as well as the causes underlying the differential expression of GSTs are also reviewed. The regulation of GST gene transcription is an area subject to active research (Rushmore and Pickett, 1993; Daniel, 1993; Hayes and Pulford, 1995), but considered to be outside the scope of this chapter.
