Molecular cloning and characterization of human glutathione S-transferases

Abstract

Glutathione S-Transferases (GSTs) are abundant proteins that function principally in detoxification, intracellular binding and transport. Mammalian cytosolic GSTs may be subdivided into three different classes designated as {dollar}\alpha{dollar}, {dollar}\mu{dollar} and {dollar}\pi{dollar}. The {dollar}\mu{dollar}-class GSTs have higher activity with selective groups of chemical carcinogens and toxins, such as benzo(a)-pyrene-4,5-oxide and styrene 7-8-oxide, as substrates. As a result of a gene deletion, approximately 50% of the human population is missing the hepatic {dollar}\mu{dollar}-class GST. This half of the population may be more susceptible to chemical carcinogens and drug toxicity. Our objectives were: (i) to determine effects of this gene deletion in extrahepatic tissues such as brain and testis where ordinarily the {dollar}\mu{dollar}-class GSTs are major forms; (ii) to determine if the hepatic {dollar}\mu{dollar}-class GST form is also present in other tissues; and (iii) to apply molecular cloning methods for characterization of multiple GSTs in extrahepatic tissue and the genes that encode them. (Abstract shortened with permission of author.).