Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide.
Fibroblasts from patients with hereditary cutaneous malignant melanoma are abnormally sensitive to the mutagenic effect of simulated sunlight and 4-nitroquinoline 1-oxide.
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遗传性皮肤恶性黑色素瘤患者的成纤维细胞对模拟阳光和 4-硝基喹啉 1-氧化物的诱变作用异常敏感。
DOI：
10.1073/pnas.81.4.1179
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发表时间：
1984
影响因子：
11.1
通讯作者：
McCormick,JJ
中科院分区：
文献类型：
--
作者：
Howell,JN;Greene,MH;Corner,RC;Maher,VM;McCormick,JJ
由于突变和致癌之间可能存在病因学联系，我们比较了几例遗传性皮肤恶性黑色素瘤和发育不良痣综合征患者皮肤活检组织中的成纤维细胞对广谱模拟阳光和UV模拟致癌物4-硝基喹啉1-氧化物（4 NQO）的致突变和/或细胞毒性作用的敏感性。遗传标记是对6-硫鸟嘌呤的抗性;细胞毒性试验是菌落形成能力的丧失。所有五个测试菌株比正常更敏感的4 NQO的杀伤效果（生存曲线的斜率是2至3倍陡峭），但只有一个菌株是超敏感的杀死太阳灯辐射。检测了两种菌株的致突变性。每种药物对这些药物致突变作用的反应与其对细胞杀伤的反应一致。这两种菌株暴露于4 NQO后都是超变的，但只有一个显示出高于正常频率的突变体诱导的模拟阳光。恶性黑色素瘤遗传变异患者的非恶性成纤维细胞对致癌物诱导的突变异常敏感，这一发现表明对诱变剂的超敏反应有助于患者患黑色素瘤的风险。它也支持癌症起源的体细胞突变假说。
Because of a possible etiologic link between mutations and carcinogenesis, we compared fibroblasts derived from skin biopsies of several patients with hereditary cutaneous malignant melanoma and the dysplastic nevus syndrome for sensitivity to the mutagenic and/or cytotoxic effect of broad-spectrum simulated sunlight and of a UV mimetic carcinogen, 4-nitroquinoline 1-oxide (4NQO). The genetic marker was resistance to 6-thioguanine; loss of colony-forming ability was the assay for cytotoxicity. All five strains tested were more sensitive than normal to the killing effect of 4NQO (slopes of survival curves were 2- to 3-fold steeper), but only one strain was hypersensitive to killing by Sun Lamp radiation. Two strains were tested for mutagenicity. The response of each to the mutagenic action of these agents corresponded to its response to cell killing. Both strains were hypermutable after exposure to 4NQO, but only one showed a higher than normal frequency of mutants induced by simulated sunlight. The finding that nonmalignant fibroblasts from patients with a hereditary variant of malignant melanoma are abnormally susceptible to carcinogen-induced mutations suggests that hypersensitivity to mutagens contributes to risk of melanoma in patients. It also supports the somatic cell mutation hypothesis for the origin of cancer.