Influence of catalase on the radiosensitivity of Fanconi anemia lymphocytes in vitro

Abstract

Fanconi anemia (FA) is a genetic disease characterized by progressive pancytopenia and cancer susceptibil?ity. The clinical and cellular phenotypes of Fanconi anemia are associated with a set of redox abnormalities, indicating that FA is an oxidative stress-related disorder. Fanconi anemia cells are highly sensitive to DNA clastogen agents, but their response to ionizing radiation is still unclear. The aim of this study was to evaluate the in vitro radiosensitivity of Fanconi anemia homozygotes and heterozygotes, and to assess the contribution of catalase and superoxide dismutase (SOD) to the overall radiobiological response of the cells. The incidence of radiation-induced lymphocyte micronuclei was used as the indicator of radiation sensitivity in vitro, whereas the activity of antioxidant enzymes was determined in erythrocytes. Patients with FA exhibited a two-fold decrease in catalase activity, accompanied by lowered activity of SOD, and increased incidence of baseline micronuclei. In the entire group of patients (with one exception), a reduced yield of radiation-induced micronuclei in lymphocytes was observed, and this was categorized as a radioresistant response. A mild radioresistant in vitro response was also observed in carrier-mothers, accompanied by reduced activity of catalase. The radiosensitivity of carrier-fathers was normal. The results of this study suggest that reduced activity of catalase is an important contributor to the radiobiological response of cells.