The assessment of radiosensitivity in patients with ataxia-telangiectasia syndrome and in carriers of the mutated ATM gene using lymphoblastoid cell lines

Abstract

Introduction: Hypersensitivity to ionising radiation is most often observed in the course of primary immunodeficiency diseases, which are associated with dysfunctional DNA repair, especially with the repair of double-strand breaks. Due to phenotypic similarities between primary immunodeficiency diseases, radiosensitivity testing can prove useful in early differential diagnosis, when attempting to identify patients with increased toxic reactivity to radio- and chemotherapy, and can have an impact on the process of their preparation for stem cell transplantation. Aim: The aim of the study was to assess the radiosensitivity in vitro of patients with ataxia-telangiectasia (A-T) syndrome, and their parents, carriers of one copy of the mutated ATM gene. Material/Methods: Lymphoblastoid cell lines (LCLs) from 15 A-T patients (remaining under the care of the Immunology Clinic and Immunology Outpatient Clinic of the Children’s Memorial Health Institute) and 11 mothers and 11 fathers of A-T patients, were used for radiosensitivity assessment. A standard colony survival assay (CSA) was applied in the tests. Results: A markedly decreased survival fraction (SF) of LCLs after in vitro exposure to X-rays was observed in all A-T patients when compared to control cells. A clear diversification of radiosensitivity to ionising radiation was observed among obligate heterozygotes. SF for heterozygotes was between 1% and 53%, i.e. varied from the values in healthy individuals to the extreme values observed in A-T patients. Conclusion: The assessment of cell radiosensitivity in A-T patients using CSA may be a useful additional test for confirming a clinically suspected disease. In heterozygous carriers, it can be an indicator of increased risk of carcinogenesis, and in both A-T patients and their parents can be helpful in making decisions with regard to radio- and/or chemotherapy.