CULTURED DIPLOID FIBROBLASTS FROM PATIENTS WITH THE NEVOID BASAL-CELL CARCINOMA SYNDROME ARE HYPERSENSITIVE TO KILLING BY IONIZING-RADIATION

  • 1 January 1983
    • journal article
    • research article
    • Vol. 111  (1) , 50-55
Abstract
Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disease. About 20% of the gene carriers studied developed medulloblastoma before the age of 5 yr. Clinical follow-up of these patients, treated with radiotherapy, revealed a predisposition to radiogenic basal cell carcinomas with an unusually short latent period of 6 mo.-3 yr. Skin fibroblasts were cultured from 5 NBCCS patients and measured their radiosensitivity in terms of clonogenic survival. Compared with 6 normal controls, the NBCCS cells were hypersensitive to X-rays. The average D0 (the inverse of the slope of the survival curve) for the NBCCS cells was 98 rads, compared with 142 rads for the normal controls and 44 rads for an ataxia telangiectasia (AT) strain. The average D10 values (the dose required to reduce survival to 10%) were 258, 351 and 123 rads for the NBCCS, normal and AT strains, respectively. Unscheduled DNA synthesis measurements showed that NBCCS cells were not defective in excision repair of X-ray-damaged DNA. Pulse labeling index measurements showed that NBCCS cells were abnormally inhibited in the initiation of DNA synthesis following X-irradiation. The mechanisms underlying the radiosensitivity of NBCCS differ in several respects from those of AT. NBCCS appears to be potentially a useful model for studying the cellular processes that are important in radiation carcinogenesis.