Can an extremely elevated radiosensitivity in patients be recognized by the in-vitro testing of lymphocytes?

BACKGROUND: We have examined the in-vitro radiosensitivity of lymphocytes in patients with extreme acute and chronic reactions after curative radiotherapy under the assumption of increased genetic radiosensitivity. PATIENTS AND METHODS: 16 patients (14 females, 2 males, age 40 to 69 years) were retrospectively examined 1 to 108 months after radiotherapy. All had undergone definitive or postoperative curative radiotherapy for cancer (12 breast cancer, 2 lung, 1 bladder, and 1 head and neck cancer). None of them had known genetic disorders with increased radiosensitivity. Four patients were considered as having probably increased radiosensitivity; they had shown poor tolerance to radiotherapy (1 severe acute reaction with cessation of radiotherapy in bladder cancer and subsequent bladder shrinkage after 45 Gy, 1 acute skin reaction well above average with subsequent fibrosis after irradiation for regional recurrence of breast cancer, 1 radiation myelitis after palliative irradiation with 5 x 5 Gy for lung cancer, 1 severe acute reaction after mediastinal irradiation for lung cancer). Twelve patients were considered as having normal tolerance to radiotherapy. They had tolerated radiotherapy well with normal acute reactions and no or minimal signs of late radiation sequelae. Lymphocyte cultures were prepared from all patients and irradiated with 0.7 and 2 Gy, respectively; 1 culture served as control (0 Gy). Chromosomes 1, 2, and 4 were stained using fluorescence in-situ hybridization (FISH) with a 3-colour-chromosome-in-situ suppression technique. Chromosomal breaks were counted in 200 to 1000 mitoses. Radiation sensitivity was expressed as radiation-induced breaks per mitoses corrected for breaks at 0 Gy. The probes were coded and the examiner did not know the clinical course. RESULTS: Significant differences in interindividual radiation sensitivity were detectable. The frequency of radiation-induced breaks/1000 mitoses ranged from 70 to 556 after 0.7 Gy and from 420 to 1210 after 2 Gy. The 4 patients with increased clinical radiation sensitivity showed also increased chromosomal radiation-induced damage as compared to the 12 patients with normal radiation tolerance (469 +/- 103 vs. 126 +/- 79 breaks/1000 mitoses induced by 0.7 Gy, p = 0.0011, and 864 +/- 258 vs. 574 +/- 119 breaks/1000 mitoses induced by 2 Gy, p = 0.019). CONCLUSIONS: Patients with increased clinical radiosensitivity exhibited increased chromosomal damage in lymphocytes in vitro measured with chromosome painting with a FISH-technique. This technique may be useful to detect patients with severely enhanced radiosensitivity. The results suggest that if radiosensitivity is abnormally elevated this may be present and detectable in different organs.