IMMUNOHISTOCHEMICAL LOCALIZATION OF GLUTATHIONE S-TRANSFERASES IN HUMAN LUNG

Glutathione S-transferases (GST) detoxify a number of carcinogenic ele ctrophiles including diol-epoxide metabolites of polycyclic aromatic h ydrocarbons. The distribution of GSTs A1/A2, M1, M2, M3, and P1 has be en studied in lung tissue from 32 subjects by immunohistochemistry usi ng rabbit polyclonal antibodies. GSTA1/A2 and GSTP1 were found to be t he most abundant GSTs in human lung, being present in the bronchial an d bronchiolar epithelium of all individuals studied. The staining inte nsity for GSTA1/A2 varied more than that for GSTP1 between individuals . GSTM1, a polymorphic mu-class enzyme, was ambiguously detected in lu ng tissue and, if expressed, is present at very low levels. GSTM2, a s triated muscle-specific isozyme, occurred minimally in the epithelium of the terminal airways, and GSTM3, an enzyme of broad extrahepatic oc currence, was observable in the ciliated airway epithelium and smooth muscle of the lung. The staining for GSTM3 varied from minimal to very intense between individuals; in the bronchial epithelium, it was more abundant in current smokers than in exsmokers. The immunostaining for GSTs in general was most intense in the bronchial epithelium decreasi ng in the distal airways, in contrast to the previously described peri pheral localization of the polycyclic aromatic hydrocarbons activating the P450IA1 enzyme. The localization of GSTs in the bronchial wall su ggests that GST polymorphisms may contribute to susceptibility, especi ally to bronchial tumors of tobacco smokers.