Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells
Impaired removal of 8-hydroxydeoxyguanosine induced by UVB radiation in naevoid basal cell carcinoma syndrome cells
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DOI：
10.1111/j.1365-2133.2005.06970.x
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发表时间：
2005-12-01
影响因子：
10.3
通讯作者：
Miyachi, Y
中科院分区：
文献类型：
--
作者：
Nishigori, C;Arima, Y;Miyachi, Y
背景痣样基底细胞癌综合征（NBCCS）是一种常染色体显性遗传疾病，以多发性基底细胞癌、牙源性角化囊肿等肿瘤发生和硬脑膜皱褶钙化、肋骨畸形等发育异常为特征。最近，已经表明紫外线（UV）B暴露在ptch敲除小鼠中比野生小鼠产生更多的BCCs.Objectives为了研究UV在NBCCS中BCCs发展中的作用，使用来自NBCCS患者的成纤维细胞在生理相关剂量的UVB暴露下检测细胞对UVB杀伤的敏感性和UVB诱导的氧化DNA损伤的去除。通过光生物学分析检查了一名59岁男性患者、一名18岁男孩和一名13岁男孩。使用来自这些患者的成纤维细胞测试细胞对UVB和UVC杀伤的敏感性以及UVB引起的氧化DNA损伤的去除。我们测量细胞8-羟基脱氧鸟苷（8-OHdG）后，UVB暴露后24 h UVB exposure using high performance liquid chromatography.Results所有三个细胞株来自患者NBCCS是超敏感的UVB（D-10：50-70%正常），但不是由UVC杀死。UVB照射后，NBCCS细胞和正常细胞中8-OHdG的产生量均呈剂量依赖性增加，直至3200 μ m（-2）。在正常细胞中，UVB照射后24小时内8-OHdG恢复到其基础水平，而在NBCCS细胞中，800 Jm（-2）UVB照射后8-OHdG的量即使在24小时后也没有恢复到其基础水平。结果表明，NBCCS细胞对8-OHdG的清除能力可能受到损害。NBCCS细胞清除胸腺嘧啶二聚体的能力与正常细胞相似。结论UVB超敏反应可作为NBCCS临床特征尚未完善者的诊断工具之一。对细胞杀伤的超敏反应和UVB暴露后8-OHdG的清除受损可能在NBCCS中发生BCC和其他肿瘤中发挥一定作用。
Background The naevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder characterized by tumorigenesis such as multiple basal cell carcinomas, odontogenic keratocysts and developmental abnormalities such as calcified dural folds and rib-anomalies. Recently, it has been shown that ultraviolet (UV) B exposure produced more BCCs in ptch knockout mice than wild mice.Objectives To Investigate the role of UV in development of BCCs in NBCCS, cellular sensitivity to killing by UVB and removal of UVB-induced oxidative DNA damage were examined using fibroblasts derived from patients with NBCCS under physiologically relevant doses of UVB exposure,Patients and methods Three patients with NBCCS, a 59-year-old male patient, an 18-year-old boy and a 13-year-old boy were examined by photobiological analysis. Cellular sensitivity to killing by UVB and UVC and removal of oxidative DNA damage caused by UVB were tested using fibroblasts derived from these patients. We measured cellular 8-hydroxydeoxyguanosine (8-OHdG) after UVB exposure up to 24 h after UVB exposure using high-performance liquid chromatography.Results All three cell strains derived from the patients with NBCCS were hypersensitive to killing by UVB (D-10: 50-70% of normal) but not by UVC. After UVB exposure, the production of 8-OHdG increased dose dependently up to 3200 Jm(-2) in both NBCCS cells and normal cells. In normal cells, 8-OHdG after UVB exposure returned to its basal level during 24 h, whereas in NBCCS cells the amount of 8-OHdG after 800 Jm(-2) of UVB exposure did not return to its basal level even after 24 h. The result indicates the removal of 8-OHdG could be impaired in NBCCS cells. Ability in removal of thymine dimers of NBCCS cells was similar to that of normal cells.Conclusions Hypersensitivity to UVB can be one of the diagnostic tools of NBCCS for those whose clinical features have not yet completed. Hypersensitivity to cell killing and the impairment of removal of 8-OHdG after UVB exposure may play some role in developing BCCs and other tumours in NBCCS.