Chan G L, Little J B
Am J Pathol. 1983 Apr;111(1):50-5.
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 years. 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 months to 3 years. The authors have therefore cultured skin fibroblasts from 5 NBCCS patients and measured their radiosensitivity in terms of clonogenic survival. Our results showed that, 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.
痣样基底细胞癌综合征（NBCCS）是一种常染色体显性疾病。在接受研究的基因携带者中，约20%在5岁前发生了髓母细胞瘤。对这些接受放射治疗的患者进行临床随访发现，他们易患放射性基底细胞癌，潜伏期异常短，为6个月至3年。因此，作者培养了5例NBCCS患者的皮肤成纤维细胞，并根据克隆形成存活率测量了它们的放射敏感性。我们的结果显示，与6名正常对照相比，NBCCS细胞对X射线高度敏感。NBCCS细胞的平均D0（存活曲线斜率的倒数）为98拉德，而正常对照为142拉德，共济失调毛细血管扩张症（AT）细胞株为44拉德。NBCCS、正常和AT细胞株的平均D10值（使存活率降至10%所需的剂量）分别为258、351和123拉德。非计划DNA合成测量显示，NBCCS细胞在X射线损伤DNA的切除修复方面没有缺陷。脉冲标记指数测量显示，NBCCS细胞在X射线照射后DNA合成的起始阶段受到异常抑制。NBCCS放射敏感性的潜在机制在几个方面与AT不同。NBCCS似乎可能是研究辐射致癌过程中重要细胞过程的有用模型。
