Glutathione S-transferase π-isoform is not altered in bladder tissue from smokers

Abstract

Glutathione S-transferase π (GSTπ)-isoform is a cytosolic enzyme involved in the detoxification of reactive metabolites generated from environmental pollutants and cigarette smoke. Although cigarette smoking has been implicated in the etiology of bladder cancer, no information yet exists regarding GSTπ in smokers and nonsmokers. This study was carried out to evaluate the immunohistochemical localization and to measure levels of immunoreactive GSTπ in bladder tissue from smokers and nonsmokers. Tissues from patients diagnosed with transitional cell carcinoma (TCC) were obtained from paraffin embedded blocks fixed in formalin. Bladder tissues from smokers (n = 7) and nonsmokers (n = 8), and histologically confirmed cancerous and noncancerous areas of the same patients (n = 10) were studied. The immunoreactive GSTπ was quantified by calculating its optical density with a computerized Olympus BH-2 microscope connected to a DAGE camera. Immunohistochemical staining for GSTπ appeared to be evenly distributed in the cytosol of the transitional epithelium (TE) of the noncancerous regions. In the TE from patients with advanced TCC, the staining intensity appeared to be stronger in the nuclei relative to cytoplasm, an effect that was even more pronounced in poorly differentiated cancers and in cancers with squamoid features. The immunoreactive levels of GSTπ in the superficial TE cells was approximately 1.7-fold higher compared with the rest of the TE layer (p < 0.05) in smokers and nonsmokers. No significant differences (p > 0.05) were observed between smokers and nonsmokers in either of these regions. The higher concentration of GSTπ in the TE is suggestive of the protective role of this enzyme, serving to prevent any potentially harmful xenobiotics from entering the bladder tissue. The lack of differences in the detoxifying enzymes between smokers and nonsmokers suggests that the increased susceptibility of bladder cancer in smokers is probably mediated by other mechanisms.