Enhanced radiosensitivity and defective DNA repair in cultured fibroblasts derived from Rothmund Thomson syndrome patients

Abstract

Rothmund Thomson syndrome (RTS) is an oculocutaneous and cancer-prone disorder in which enhanced carcinogen sensitivity, mediated through abnormal DNa metabolism, may be an associated factor. Cultured fibroblasts from 5 RTS patients have been examined for their colony-forming abilities and DNa repair capacities following gamma-irradiation. 2 of the 4 RTS strains showed enhanced sensitivity following hypoxic gamma-irradiation, and 1 of these 2 strains also showed enhanced sensitivity under toxic conditions. Defective DNA repair was implicated in the above abnormal responses to gamma-radiation since both strains displayed reduced levels of repair synthesis and slow removal of radiogenic DNA lesions (assayed by their sensitivity to strand-incising activities present in protein extracts of Micrococcus luteus cells). A hypothesis is presented to rationalize the origin and heterogeneity of these laboratory phenotypes of RTS.