Glutathione S-transferases and iododeoxyuridine labelling index during chemotherapy of gastric cancer

Background: Resistance to chemotherapeutic agents is a major problem in the treatment of patients with gastric cancer. Many factors may play a role in the resistance to cytotoxic drugs. The purpose of this study was to invest igate the significance of glutathione (GSH), glutathione S-transferases (GS Ts) and cell proliferation as parameters for response and resistance to che motherapy in patients with gastric cancel: Methods: In endoscopic biopsies of normal and malignant gastric tissue from 15 patients with gastric cancer treated by chemotherapy, the GSH content, GST activity and levels of GST A lpha, Mu and Pi isoenzymes were determined before the start of chemotherapy and after 2 and 6 cycles. Furthermore, cell proliferation was determined i n these biopsies after in vivo Iododeoxyuridine (IdU) labelling. Results: N one of the above mentioned parameters were predictive for response to chemo therapy. After 2 courses of chemotherapy there was an increase of median GS H content (367%) in three patients with partial response (PR) whereas there was a decrease (43%) in five patients with progressive disease (PD) (p<0.0 5). Median GST activity increased (257%) in patients with PR and declined ( 31%) in patients with PD (p<0.05). GST Pi showed a median increase of 326% in responding patients and a 59% decrease in progressive patients (p < 0.05 ). There were no significant changes in GST Alpha and Mu. In seven patients with stable disease (SD) there were no significant changes in GSH/GST para meters. Conclusion: GSH/GST parameters and IdU labelling index determined b efore the start of chemotherapy were not predictive for response to that ch emotherapy. However, the differences of GSH and GST parameters between resp onding and progressive patients suggests a role for the GSH/GST system in t he susceptibility of gastric tumor cells to chemotherapy.