FREQUENCY OF ULTRAVIOLET LIGHT-INDUCED MUTATIONS IS HIGHER IN XERODERMA PIGMENTOSUM VARIANT CELLS THAN IN NORMAL HUMAN CELLS
FREQUENCY OF ULTRAVIOLET LIGHT-INDUCED MUTATIONS IS HIGHER IN XERODERMA PIGMENTOSUM VARIANT CELLS THAN IN NORMAL HUMAN CELLS
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DOI：
10.1038/261593a0
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发表时间：
1976-01-01
期刊：
影响因子：
64.8
通讯作者：
MCCORMICK, JJ
中科院分区：
文献类型：
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作者：
MAHER, VM;OUELLETTE, LM;MCCORMICK, JJ
患有遗传性疾病着色性干皮病（XP）的患者在暴露于阳光的区域易患多发性皮肤癌1。来自这些患者中的大多数（经典XP）的皮肤的成纤维细胞已被证明在由紫外线辐射诱导的DNA损伤的切除修复中有缺陷1 -3。然而，一组患者被称为“XP变体”，因为尽管他们患有该疾病的临床表现，但他们对DNA 4 -6的这种紫外线损伤进行了正常的切除修复。Lehmannet等6报道，来自这种XP变体的细胞在将紫外线照射后合成的初始低分子量DNA转化为大小与未照射细胞中产生的DNA相似的高分子量DNA方面异常缓慢。虽然这些作者认为这种异常的DNA复制可能解释了为什么这些患者容易患皮肤癌，但他们没有提出任何机制。如果由Boveri首次提出的关于癌症起源的体细胞突变假说是正确的，那么人们可以预期，在来自经典和变异XP患者的皮肤活检的细胞中，紫外线诱导的突变频率高于来自正常人的细胞。为了验证这一假设，我们进行了一系列定量研究，比较了正常人皮肤成纤维细胞中紫外线诱导突变对氮鸟嘌呤耐药性的频率，以及经典和变异XP衍生的各种菌株中的频率。我们已经发现，来自两种XP患者的细胞确实显示出比正常细胞高得多的频率。将两种经典XP菌株与正常细胞进行比较的数据已发表8，9。在这里，我们提出的数据与变异株，XP 4 BE。
PATIENTS with the inherited disease, xeroderma pigmentosum (XP), are subject to multiple carcinomas of the skin on areas exposed to sunlight1. Fibroblasts from the skin of the majority of these patients (classical XP) have been shown to be deficient in excision repair of lesions induced in DNA by ultraviolet radiation1–3. One group of patients, however, has been designated ‘XP variants’ because, although they suffer the clinical manifestations of the disease, they carry on normal excision repair of such ultraviolet-light damage to DNA4–6. Lehmannet al.6reported that cells from such XP variants are abnormally slow in converting initially low molecular weight DNA, synthesised after ultraviolet irradiation, into high molecular weight DNA similar in size to that produced in unirradiated cells. Although these authors suggest that such abnormal DNA replication might explain why such patients are susceptible to cancer of the skin, they do not propose any mechanism. If the somatic cell mutation hypothesis on the origin of cancer, first suggested by Boveri7, is correct one would expect the frequency of mutations induced by ultraviolet light to be higher in cells derived from skin biopsies from both classical and variant XP patients than in cells from normal persons. To test this hypothesis, we have carried out a series of quantitative investigations comparing the frequency of ultraviolet-light induced mutations to azaguanine resistance in normal human skin fibroblasts with that found in various strains derived from classical and variant XPs. We have found that cells derived from both kinds of XP patients indeed show much higher frequencies than normal cells. The data comparing two classical XP strains with normal cells have been published8,9. Here, we present data obtained with variant strain, XP4BE.