ABSENCE OF ATM TRUNCATIONS IN PATIENTS WITH SEVERE ACUTE RADIATION REACTIONS

Purpose: Severe acute toxicity limits the effective use of radiotherap y in patients who are radiosensitive, and it is not usually possible t o identify these radiohypersensitive (R-H) individuals before treatmen t commences. Five such R-H patients were detected over a 3-year period . We undertook this study to determine whether the severe acute radioh ypersensitivity of these five individuals showed any correlation with cellular and molecular parameters known to be abnormal in radiosensiti vity-related syndromes such as ataxia-telangiectasia (A-T), Methods an d Materials: Lymphoblastoid cells were isolated from fresh blood from the 5 R-H individuals who had previously demonstrated clinical R-H at least 9 months prior to sampling. Lymphoblastoid cell lines (LCLs) wer e established to determine the extent of postradiation chromosomal abe rrations, cell cycle delay, cell proliferation, and tumor suppressor p 53 protein stabilization. The polymerase chain reaction (PCR) and prot ein truncation (PTT) assays were used to test for the possibility of m utations in the gene mutated in A-T, termed ATM, Results: LCLs derived from R-H subjects retained a significantly higher degree of radiation -induced chromosomal aberrations when compared to normal control LCLs, p53 stabilization by ionizing radiation appeared normal in all but on e R-H subject. There was no evidence of A-T gene truncation mutations in any of the R-H subjects tested. Conclusions: All R-H subjects in th is study had their cellular radiosensitivity confirmed by the chromoso mal aberration assay. Delayed p53 stabilization at 4 hours postirradia tion in one R-H subject suggested that different etiologies may apply in the radiohypersensitivity investigated in this study. (C) 1998 Else vier Science Inc.