Increased radiosensitivity of a subpopulation ot T-lymphocyte progenitors from patients with Fanconi's anemia
Knox, S.J.; Wilson, F.D.; Greenberg, B.R.; Shifrine, M.; Rosenblatt, L.S.; Reeves, J.D.; Misra, H.
Blood 57(6): 1043-1048
ISSN/ISBN: 0006-4971 PMID: 6971665 Accession: 005664827
In vitro radiation survival of peripheral blood T lymphocytes was studied in 15 clinically normal adults and 4 patients with Fanconi's anemia. Tritiated thymidine incorporation in a whole blood lymphocyte stimulation test (LST) and a newly developed whole blood T-lymphocyte colony assay were used to measure lymphocyte blastogenesis and colony formation in response to phytohemagglutinin (PHA) or concanavalin-A (Con-A) stimulation. Lymphocyte colony formation was consistently more sensitive than the LST for detection of low-level radiation effects using normal cells and lymphocytes from Fanconi's anemia patients. Lymphocytes from patients with Fanconi's anemia were significantly more sensitive to in vitro x-irradiation than lymphocytes from clinically normal individuals as measured by their ability to divide when stimulated by PHA in the LST (patients, D37 = 198 R; normals, D37 = 309 R, P = 0.057) and colony formation assay (patients, D37 = 53 R; normals, D37 = 109 R, P = 0.016). No significant difference in the radiosensitivity of the Con-A response was observed between the 2 groups. The PHA-responsive T-lymphocyte subpopulation in Fanconi's anemia patients appears to be intrinsically defective. The nature of this defect, significance in the disease process and relevancy of these findings to the establishment of radiation protection standards are discussed. [Patients with Fanconis anemia, which is a genetic disorder, are prone to acquiring radiation-induced malignancy.].