Re-evaluation of in vitro radiosensitivity of human fibroblasts of different genetic origins.

A statistical analysis of the radiosensitivity of 204 different survival curves of nontransformed human fibroblast cell strains of different genetic origins was made using three criteria: the multi-target one-hit model (characterized by parameters n and D0), the surviving fraction for a 2 Gy dose (S2) and the mean inactivation dose (D). D is found to be the best parameter for characterization of anomalous radiosensitivity linked to a genetic disorder and for discrimination between groups of cell strains of differing radiosensitivity. Its use allows the description of a range of 'normal' radiosensitivity for control fibroblasts and the classification of the various genetic disorders as a function of their mean radiosensitivity expressed in terms of D. Nine groups of cell strains appear to exhibit radiosensitivity which differs significantly from that of the controls: seven groups are hypersensitive (ataxia-telangiectasia homozygotes and heterozygotes, Cockayne's syndrome, Gardner's syndrome, 5-oxoprolinuria homozygotes and heterozygotes, Fanconi's anaemia) and two groups are more radioresistant (fibroblasts from retinoblastoma patients and from individuals with chromosome 13 anomalies). Since the coupled parameter n and D0 failed to discriminate between the radiosensitivity of the different genetic groups, we recommend the use of D to make an intercomparison of intrinsic radiosensitivity of nontransformed human fibroblasts.