Impaired Colony-Forming Ability Following γ Irradiation of Skin Fibroblasts from Tuberous Sclerosis Patients

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Abstract
The radiosensitivity of cultured dermal fibroblasts from human subjects afflicted with tuberous sclerosis (TS), a hereditary neurocutaneous syndrome, was assessed by assaying the loss of colony-forming ability in response to acute .gamma.-ray exposure. Relative to control strains from clinically normal donors, 3 cell lines (GM1635, GM1643, GM2333) from 2 affected patients displayed enhanced sensitivity to inactivation by 60Co .gamma.-ray treatment, whether administered oxically (air-saturated) or hypoxically (N2-gassed); a 4th strain (GM1644) from a 3rd patient exhibited normal radiosensitivity under both treatment conditions. The post-.gamma.-irradiation colony-forming ability of the 3 hypersensitive TS strains was intermediate between that of normal controls and that of strains from patients inheriting the radiotherapy-sensitive neurovascular disorder ataxia telangiectasia. The variability in the radioresponse of the TS strains (3 sensitive and 1 normal) is not surprising, considering the widely recognized clinical heterogeneity in the disease. Aside from providing a laboratory marker for early (possibly presympatomatic) detection of persons at high risk for TS, these findings may lead to a better understanding of the origin and progressive development of this multifaceted syndrome.