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Institute of Occupational Health, SF-00250 Helsinki, Finland [S. A., A. H., K. H-P.]; International Agency for Research on Cancer, 69372 Lyon Cedex 08, France [H. V.]; Biomedical Research Centre, Ninewells Hospital, Dundee DD1 9SY, Scotland [J. D. H.]; and Department of Biochemistry and Molecular Biology, University College of London, London W1P 6DB, England [B. K.]
2 To whom requests for reprints should be addressed, at Institute of Occupational Health, Topeliuksenkatu 41 aA, SF-00250 Helsinki, Finland.
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 µ-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.
1 Supported by The Finnish Foundation for Cancer Research, Helsinki, Finland.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 6/ 1/93. Accepted 9/24/93.
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