Transformation and repair replication in lymphocytes from ataxia telangiectasia

Peripheral blood leukocytes (PBL) isolated from five patients with ataxia telangiectasia (AT) proved more difficult to transform following addition of exogenous Epstein-Barr virus than PBL isolated from AT heterozygotes or normal adults. PBL isolated from one AT patient transformed within the range expected for normal PBL. Once established in culture, the resulting lymphoblastoid cell lines (LCLs) were immortal and, though they grew slower than normal control LCLs, provided useful material for studying cellular phenotypes associated with AT lymphoid cell lines. All the resulting LCLs established from ataxia were more sensitive to X-irradiation than were LCLs established from controls as measured by colony formation in microtiter plates. Furthermore, X-ray-induced inhibition of semiconservative DNA synthesis in ataxia LCLs was less than that seen in normal LCLs. These results are in agreement with those obtained using cultured AT fibroblasts, indicating that in vitro transformation by exogenously added Epstein-Barr virus does not alter the phenotype of the ataxia cell as measured by these two parameters. However, no deficiency in X-ray-induced excision repair of DNA was demonstrable in LCLs established from four AT patients. Nor was there a deficiency in AT LCL host cell reactivation of herpes simplex virus X-irradiated under anoxic conditions. Taken together, these data point toward a defect in ataxia lymphoblasts other than repair enzyme(s) per se, one possibly associated with chromosomal structure, function, or modification.