Transformation of human epidermal keratinocytes with fission neutrons.
Transformation of human epidermal keratinocytes with fission neutrons.
复制标题
用裂变中子转化人表皮角质形成细胞。
DOI：
10.1093/carcin/15.12.2867
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发表时间：
1994
期刊：
影响因子：
4.7
通讯作者：
Dritschilo,A
中科院分区：
文献类型：
--
作者：
Thraves,PJ;Varghese,S;Jung,M;Grdina,DJ;Rhim,JS;Dritschilo,A
高LET辐射照射的生物效应与辐射防护和风险评估特别相关。由于大多数癌症是上皮起源的，因此更好地了解这种细胞类型中辐射诱导的致癌转化是很重要的。因此，我们已经开始研究，以确定是否永生化的人表皮角质形成细胞（RHEK）可以转化与高LET辐射。用来自Janus反应堆的0.85 MeV裂变中子的单剂量（1、10、25、50和100 cGy）处理指数生长的RHEK细胞。中子暴露导致形态改变的细胞的发展和病灶形成后6周在汇合。这些转化的培养物以增加的饱和密度生长，表现出锚定非依赖性生长，并在裸鼠体内形成肿瘤。单链构象多态性分析和DNA测序结果表明，Ha-ras、Ki-ras和N-ras基因的密码子12/13和61以及pS3抑癌基因的外显子4-9没有点突变。这些研究表明，高LET辐射（裂变中子）可以将永生化的人类上皮细胞转化为恶性表型，这种恶性表型似乎不涉及细胞p53或ras基因的突变。
The biological effects of exposures to high LET radiations have particular relevance to radiation protection and risk assessment Since most cancers are of epithelial origin, it is important to obtain a better understanding of radiationinduced oncogenic transformation in this cell type. Accordingly we have initiated studies to determine whether immortalized human epidermal keratinocytes (RHEK) can be transformed with high LET radiations. Exponentially growing RHEK cells were treated with single doses (1, 10, 25, 50 and 100 cGy) of 0.85 MeV fission neutrons from the Janus reactor. Neutron exposure led to the development of morphologically altered cells and foci formation after 6 weeks at confluence. These transformed cultures grew with an increased saturation density, exhibited anchorageindependent growth and formed tumors hi athymlc mice. Single-strand conformatlonal polymorphism analysis and DNA sequencing demonstrated the absence of point mutations in codons 12/13 and 61 in the Ha-ras, Ki-ras, or N-rasgenes and exons 4–9 of thepS3 tumor suppressor gene. These studies demonstrate that high LET radiations (fission neutrons) can transform immortalized human epithelial cells to a malignant phenotype that does notappear to involve mutations in either the cellular p53 or ras genes.