Immunohistochemical localization of glutathione S-transferases in human lung.
Glutathione S-transferases (GST) detoxify a number of carcinogenic electrophiles including diol-epoxide metabolites of polycyclic aromatic hydrocarbons. The distribution of GSTs A1/A2, M1, M2, M3, and P1 has been studied in lung tissue from 32 subjects by immunohistochemistry using rabbit polyclonal antibodies. GSTA1/A2 and GSTP1 were found to be the most abundant GSTs in human lung, being present in the bronchial and bronchiolar epithelium of all individuals studied. The staining intensity for GSTA1/A2 varied more than that for GSTP1 between individuals. GSTM1, a polymorphic mu-class enzyme, was ambiguously detected in lung tissue and, if expressed, is present at very low levels. GSTM2, a striated muscle-specific isozyme, occurred minimally in the epithelium of the terminal airways, and GSTM3, an enzyme of broad extrahepatic occurrence, 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 decreasing in the distal airways, in contrast to the previously described peripheral localization of the polycyclic aromatic hydrocarbons activating the P450IA1 enzyme. The localization of GSTs in the bronchial wall suggests that GST polymorphisms may contribute to susceptibility, especially to bronchial tumors of tobacco smokers.
Anttila
S
S
Institute of Occupational Health, Helsinki, Finland.
Hirvonen
A
A
Vainio
H
H
Husgafvel-Pursiainen
K
K
Hayes
J D
JD
Ketterer
B
B
D000328:Adult; D000368:Aged; D005260:Female; D005982:Glutathione Transferase / Q000032:analysis* / Q000235:genetics / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000032:analysis*; D008168:Lung / Q000201:enzymology*; D008297:Male; D008875:Middle Aged
D007527:Isoenzymes; D005982:Glutathione Transferase