Gene structure and regulation of expression of human glutathione S-transferases alpha.

Current knowledge on the structure of human alpha-class glutathione S-transferase (GST) genes and the regulation of their expression is reviewed. The alpha-class GST comprises several genes and pseudogenes localised in a tight cluster on chromosome 6. Although the human GSTA1 and GSTA2 genes have the same number of exons and introns as their rat and mouse counterparts, the sequences of the 5'-flanking regions of the human alpha-class genes are significantly different from the rodents, suggesting different mechanisms of regulation between human and rodents. The expression of GST alpha is altered in a variety of tumors and several lines of evidence implicate the alpha-class GSTs in chemotherapeutic drug resistance. Finally, the induction of human GSTs by drugs or nutritional constituents would justify an interest for developing chemointervention strategies in populations highly exposed to carcinogens like aflatoxin B1 and polycyclic aromatic hydrocarbons.