Increased radiosensitivity of a subpopulation ot T-lymphocyte progenitors from patients with Fanconi's anemia

Abstract

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 found to be consistently more sensitive than the LST for detection of low-level radiation effects using both 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 two 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.

Evaluation of testicular degeneration induced by low‐frequency electromagnetic fields

“…The wide variety of responses in both tumor and normal tissues following radiotherapy are mainly related to differences in radiosensitivity (Tang et al, 2008). According to Knox et al (1981), genetic and environmental factors may predispose certain humans to radiation-induced malignancies.…”

Unravelling the web of DNA repair disorders

“…Fanconi's anaemia, a genetically heterogeneous disorder characterized by severe aplastic anaemia and developmental abnormalities is associated with mitomycin C (MMC) sensitivity. Radiosensitivity in FA cell lines has until recently been inconsistently reported [12,13]. However, a rare variant due to a mutation in the FAND2 gene shows an overlap with NBS, and patients present with early features of immunodeficiency and cell lines show sensitivity to IR [14].…”

“…A role for NBS1 in NHEJ in mammalian cells has not been established although recent evidence hints at a role for the Mre11/NBS/RAD50 complex in a cell free system [25]. Fanconi's anaemia has not conventionally been associated with radiation sensitivity disorders, although radiosensitivity is occasionally reported [12,13]. However, recent reports have described the physical convergence of several DNA damage response signalling components which has proved useful in understanding some of the clinical features of distinct complex disorders such as A‐T, NBS and FA.…”

Recurrent aphthous ulcers in Fanconi's anaemia: a case report

“…Some patients with FA have no physical abnormalities [2,3]. The disease often appears in the first decade of life, with a mean age of onset of 6·5 years [4,5]. Patients with FA often present with symptoms related to thrombocytopenia and neutropenia, such as cutaneous bleeding and infections.…”