RADIATION-INITIATED, IMMORTAL SYRIAN-HAMSTER EMBRYO FIBROBLASTS RELEASE ELEVATED LEVELS OF H2O2 AND SHOW DIVERGENT MNSOD AND CATALASE ACTIVITIES

To characterize molecular events associated with the neoplastic conver sion of primary cells by ionizing radiation, we studied the activities and mRNA expression of manganese superoxide dismutase (MnSOD) and cat alase (CAT) in Syrian hamster embryo fibroblasts during the early stag es of immortalization after treatment with gamma-rays. The irradiated cells showed divergent MnSOD and CAT responses relative to unirradiate d controls. At passage 6, MnSOD activity was increased about 50-fold, although the concentration of MnSOD mRNA increased only 1.6-fold. By c ontrast, CAT activity diminished 2-fold despite an increase of 1.6-fol d in the concentration of CAT mRNA. This divergence between the MnSOD and CAT activities was maintained upon culturing and, at passage 12, M nSOD was 35-fold increased and CAT 3.7-fold decreased, relative to uni rradiated cells. The amount of H2O2 released into the culture medium b y the radiation-initiated cells was 6-fold greater than in control med ia. Because H2O2 is a causative agent in the induction of malignant tr ansformation in vitro, our results suggest that the elevated productio n of H2O2 caused by the imbalance between the activities of MnSOD and CAT may participate in the immortalization and subsequent malignant co nversion of Syrian hamster embryo fibroblasts by ionizing radiation.