IMMUNOHISTOCHEMICAL LOCALIZATION OF GLUTATHIONE S-TRANSFERASE-T1 IN MURINE KIDNEY, LIVER, AND LUNG

Glutathione S-transferase-mediated metabolism of exogenous compounds u sually leads to detoxification, but there are some exceptions. For exa mple, glutathione S-transferase-TI (GSTT1) can also generate genotoxic metabolites, Studies on the biology of GSTT1 are limited by the lack of specific antibodies recognizing GSTT1 in animal tissues. We localiz ed GSTT1 immunohistochemically in mouse kidney? liver, and lung using a novel antibody targeted against the C-terminus of rat GSTTI (rGSTT1) . The antibody was characterized using immunoblot and shown to specifi cally recognize rGSTT1 and mouse GSTTI, but not human GSTTI. In kidney , GSTT1 staining was detected only in collecting duct epithelium. In l iver, pericentral hepatocytes showed cytoplasmic and nuclear staining. Nuclear staining was also observed in several other hepatocytes witho ut relation to liver zonation. Nuclei and supranuclear cytoplasm of bi le duct epithelium and endothelium of interlobular arterioles also rea cted strongly. In lung, staining was observed in bronchiolar epitheliu m and in surrounding muscle cells. Type II pneumocytes and endothelial cells of intrapulmonary capillaries also showed strong positive stain ing. This report describes the first immunohistochemical localization of GSTTI in mammalian tissues. The reported location of GSTTI is consi stent with its known metabolic activity toward compounds such as dichl oromethane and their metabolism into genotoxic products.