GLUTATHIONE, GLUTATHIONE-S-TRANSFERASE-ALPHA AND GLUTATHIONE-S-TRANSFERASE-PI, AND ALDEHYDE DEHYDROGENASE CONTENT IN RELATIONSHIP TO DRUG-RESISTANCE IN OVARIAN-CANCER

Glutathione, glutathione S-transferases alpha and pi, and aldehyde deh ydrogenase are associated with resistance to carboplatin and/or cyclop hosphamide in cell lines. Therefore, we examined whether the expressio n of these factors in ovarian cancer tissue specimens is associated wi th resistance of the patients to combination chemotherapy with cycloph osphamide/carboplatin. Ovarian cancer tissue specimens were taken intr aoperatively from 139 patients and frozen in liquid nitrogen, and the contents of glutathione S-transferases alpha and pi, total glutathione , and aldehyde dehydrogenase activity were determined. No association between the levels of glutathione S-transferases alpha and pi or aldeh yde dehydrogenase activity in tumor tissue and the survival time was o bserved in patients with primary ovarian cancer. Significantly higher levels of aldehyde dehydrogenase were observed in FIGO stage I and II compared to FIGO stage III and IV tumors (P = 0.019, Wilcoxon test, tw o sided). The median survival time was significantly longer in patient s with primary ovarian cancer with a tumor glutathione content of <4.9 mu g/mg protein compared to patients with a tumor glutathione content of greater than or equal to 4.9 mu g/mg protein (P = 0.047). However, glutathione was not an independent prognostic factor, but was signifi cantly associated with FIGO stage resulting in higher levels in FIGO s tage III and IV tumors than in FIGO stage I and II tumors (P = 0.0094, Wilcoxon test, two sided). In conclusion the glutathione content was associated with progression of ovarian carcinomas but neither glutathi one nor glutathione S-transferases alpha and pi or aldehyde dehydrogen ase were independent factors of resistance to cyclophosphamide/carbopl atin. (C) 1997 Academic Press.