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

• Published in: Radiation research 1982-05, Vol.90 (2), p.260-270
• Main Authors: Paterson, Malcolm C., Sell, Brenda M., Smith, Blake P., Bech-Hansen, N. Torben
• Format: Article
• Language: English
• Subjects: Ataxia telangiectasia; Cell lines; Cell Survival - radiation effects; Cobalt Radioisotopes; Colony-Forming Units Assay; Dose-Response Relationship, Radiation; Female; Fibroblasts; Fibroblasts - radiation effects; Gamma Rays; Humans; Hypersensitivity; Hypoxia; In Vitro Techniques; Irradiation; Male; Oxygen; Radiation damage; Radiation Tolerance; Skin; Skin - pathology; Tuberous sclerosis; Tuberous Sclerosis - pathology
• ISSN: 0033-7587; 1938-5404
• DOI: 10.2307/3575704

The radiosensitivity of cultured dermal fibroblasts from human subjects afflicted with tuberous sclerosis (TS), a hereditary neurocutaneous syndrome, was assessed by assaying loss of colony-forming ability in response to acute γ-ray exposure. Relative to control strains from clinically normal donors, three cell lines (GM1635, GM1643, GM2333) from two affected patients displayed enhanced sensitivity to inactivation by 60 Co γ-ray treatment, whether administered oxically (air-saturated) or hypoxically (${\rm N}_{2}\text{-gassed}$); a fourth strain (GM 1644) from a third patient exhibited normal radiosensitivity under both treatment conditions. The post-γ-irradiation colony-forming ability of the three 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 (three sensitive and one normal) is not surprising, considering the widely recognized clinical heterogeneity in the disease. Our findings, aside from providing a laboratory marker for early (possibly presymptomatic) detection of persons at high risk for TS, may lead to a better understanding of the origin and progressive development of this multifaceted syndrome.