GENE STRUCTURES 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 revi ewed. The alpha-class GST comprises several genes and pseudogenes loca lised 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 an d 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 rodent s. The expression of GST alpha is altered in a variety of tumors and s ever;sl lines of evidence implicate the alpha-class GSTs in chemothera peutic drug resistance. Finally, the induction of human GSTs by drugs or nutritional constituents would justify an interest for developing c hemointervention strategies in populations highly exposed to carcinoge ns like aflatoxin B1 and polycyclic aromatic hydrocarbons.