Frequency of UV-induced neoplastic transformation of diploid human fibroblasts is higher in xeroderma pigmentosum cells than in normal cells.
Frequency of UV-induced neoplastic transformation of diploid human fibroblasts is higher in xeroderma pigmentosum cells than in normal cells.
复制标题
着色性干皮病细胞中紫外线诱导的二倍体人成纤维细胞肿瘤转化的频率高于正常细胞。
DOI：
10.1073/pnas.79.8.2613
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发表时间：
1982
影响因子：
11.1
通讯作者：
McCormick,JJ
中科院分区：
文献类型：
--
作者：
Maher,VM;Rowan,LA;Silinskas,KC;Kateley,SA;McCormick,JJ
如果二倍体人类细胞的肿瘤转化是由致癌物诱导的突变引起的，那么在UV诱导的DNA损伤的切除修复中缺陷的细胞应该比正常细胞对UV光的转化显著更敏感。我们通过用低剂量的紫外线（254 nm）照射着色性干皮病患者（XP 7 BE，互补组D）的成纤维细胞和用高得多的剂量照射正常人的细胞，并比较转化频率与锚定独立性来测试这一假设。两组细胞均表现出转化的剂量依赖性增加，这对应于存活的剂量依赖性降低。在导致相等细胞杀伤的剂量下，锚定非依赖性细胞的频率大致相等。从琼脂中分离、繁殖并注射到X射线照射的无胸腺小鼠中的XP 7 BE和正常细胞的集落在100%的动物中产生纤维肉瘤。正常细胞照射前不久开始的DNA合成表现出高频率的锚定独立的细胞，照射细胞在早期G1显示没有增加背景。这些结果与我们观察到的紫外线诱导的6-硫代鸟嘌呤抗性突变体在这些细胞中，并支持锚定独立性的假设，DNA复制损伤的模板上诱导的突变的结果。
If neoplastic transformation of diploid human cells results from carcinogen-induced mutations, cells deficient in excision repair of UV-induced DNA damage should be significantly more sensitive to transformation by UV light than normal cells. We tested this hypothesis by irradiating fibroblasts from a xeroderma pigmentosum patient (XP7BE, complementation group D) with low doses of Uv light (254 nm) and cells from a normal person with much higher doses and comparing the frequency of transformation to anchorage independence. Both sets of cells exhibited a dose-dependent increase in transformation which corresponded to a dose-dependent decrease in survival. At doses that caused equal cell killing, the frequency of anchorage-independent cells was approximately equal. Colonies of XP7BE and normal cells isolated from agar, propagated, and injected into X-irradiated athymic mice produced fibrosarcomas in 100% of the animals. Normal cells irradiated shortly before the onset of DNA synthesis exhibited a high frequency of anchorage-independent cells; cells irradiated in early G1 showed no increase over background. These results agree with those we observed for UV induction of 6-thioguanine-resistant mutants in these cells and support the hypothesis that anchorage independence results from mutations induced by DNA replication on a damaged template.
二聚体切除率、DNA 修复复制率以及人体细胞从紫外线辐射引起的潜在致命损伤中恢复的相关性。
影响因子：
3.4
作者：
B. Konze;J. Levinson;V. Maher;J. Mccormick
通讯作者：
J. Mccormick