Journal
PHARMACOLOGY
Volume 61, Issue 3, Pages 154-166Publisher
KARGER
DOI: 10.1159/000028396
Keywords
glutathione S-transferases; genetic susceptibility; modifier genes; oxidative stress; chemical carcinogen; prostaglandin; leukotriene; basal cell carcinoma; tissue-specific expression
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Two supergene families encode proteins with glutathione S-transferase (GST) activity: the family of soluble enzymes comprises at least 16 genes; the separate family of microsomal enzymes comprises at least 6 genes. These two GST families are believed to exert a critical role in cellular protection against oxidative stress and toxic foreign chemicals. They detoxify a variety of electrophilic compounds, including oxidized lipid, DNA and catechol products generated by reactive oxygen species-induced damage to intracellular molecules. An increasing number of GST genes are being recognized as polymorphic. Certain alleles, particularly those that confer impaired catalytic activity (e.g, GSTM1*0, GSTT1*0), may be associated with increased sensitivity to toxic compounds, GST polymorphisms may be disease modifying; for example, in subgroups of patients with basal cell carcinoma or bronchial hyper-responsiveness, certain GST appear to exert a statistically significant and biologically relevant impact on disease susceptibility. Copyright (C) 2000 S. Karger AG. Basel.
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