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The aim of this study was to evaluate the endogenous alterations of the antioxidant enzymes in tumor cells and to specifically compensate the resulting changes in the levels of reactive oxygen species (ROS) to control the malignant growth. We determined and compared the activities of antioxidant enzymes and the levels of superoxide anion (O2*-) and hydrogen peroxide (H2O2) in tumor cell lines with different degrees of malignancy, paired with regard to their origin (PB/CH72T4, PDV/PDVC57, and HBL-100/MCF-7). An increase in superoxide dismutase activity and a decrease in the activities of H2O2-detoxifying enzymes, as a function of malignancy, coupled with a rise in H2O2 and a decrease in O2*- were demonstrated. Treatment of cells with exogenous catalase showed a dose-dependent inhibition of proliferation. This inhibition was also demonstrated in several cell lines of different tissue origin and species, suggesting a general role of H2O2 in cell proliferation. Moreover, stable expression of human catalase in MCF-7 cells inhibited proliferation and also reverted malignant features. We conclude that H2O2 played a crucial and general role in the regulation of proliferation and that an endogenous imbalance in antioxidant enzymes could be a relevant event in the carcinogenesis process. Fil: Policastro, Lucia Laura. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Molinari, Beatriz Lucia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Larcher, Fernando. Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas; España Fil: Blanco, Patricia. Fundación Instituto Leloir; Argentina Fil: Podhajcer, Osvaldo Luis. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Investigaciones Bioquímicas de Buenos Aires. Fundación Instituto Leloir. Instituto de Investigaciones Bioquímicas de Buenos Aires; Argentina Fil: Costa, Cristina Susana. Comisión Nacional de Energía Atómica; Argentina Fil: Rojas, Paola Andrea. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Duran, Hebe Alicia. Comisión Nacional de Energía Atómica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina |
