OXIDATIVE STRESS: RELATIONSHIP TO BLADDER CANCER PATHOGENESIS

Abstract

The present study was designed to describe the defensive role of antioxidant glutathione system in bladder carcinogenesis as well as to describe a panel of tumor markers helping in early prediction oftumor aggressiveness and tumor behavior.

The glutathione tripeptide levels and glutathione-S­ transferase activities in the bladder malignant tissues (n=40) were significantly elevated, while the glutathione peroxidase showed marked decreased activity as these parameters were compared with non-involved bladder tissues (n=25). The striking finding of glutathione peroxidase were explained by special nitrosation and irreversible posttranscriptional inactivation. It was noted that depressed GPX activities might induce apoptotic cell death in susceptible tissues. Although marked increase in proliferation rate that was tested by radiolabeled thymidine uptake , there was an associated increased apoptotic changes in bladder cancer tissues with the net increased growth rate. The new UBC antigen was studied in both cytosols and urine samples from bladder cancer patients. It was concluded that an imbalance of the ratio of glutathione system antioxidant activity to the oxidant and carcinogenic factors, that occur in bladder cancer tissues may play a role in the pathogenesis of bladder cancer. This imbalance may lead to changes as increased UBC cytokeratin fragments, increased apoptosis as well as increased proliferation and tumor growth.

So, a panel of GSH, GST and GPX representing the antioxidant power of the cells as well as UBC and apoptotic index versus proliferation index may be used as prognostic factors in bladder cancer patients and patient monitoring during therapy.