Haugen A, Laerum O D
J Natl Cancer Inst. 1978 Dec;61(6):1415-22.
The surface microstructure of fetal rat brain cells undergoing neoplastic transformation in long-term cell culture after a single transplacental pulse of 75 microgram N-ethyl-N-nitrosourea/g body weight to the fetal (18th day of gestation) BD IX rat was investigated by scanning electron microscopy. After about 3 weeks of culture, N-ethyl-N-nitrosourea-pretreated fetal rat brain cells showed focal proliferation of neural cells on an underlayer of flat, epithelioid cells. The neural cells exhibited varying forms of numerous dorsal ruffles and an increased number of other surface microprojections. Between the 40th and the 100th day, nodules of bipolar and multipolar neural cells were observed with a complex surface microstructure including many blebs and ruffles and an increased number of microvilli. After 100-210 days, more rapidly proliferating, morphologically altered cells formed "piled-up" foci, which resulted in a homogeneous population of cells with numerous long microvilli, large ruffles, and blebs over the whole surface. The cells retained the same altered surface structure until tumorigenicity after reimplantation into the syngeneic host was first observed (approximately 273 days). Surface alterations characteristic of the neoplastic cells were thus observable more than 100 days before the cells became tumorigenic.
对孕期第18天的BD IX胎鼠单次经胎盘注射75微克/克体重的N-乙基-N-亚硝基脲后，通过扫描电子显微镜研究了在长期细胞培养中发生肿瘤转化的胎鼠脑细胞的表面微观结构。培养约3周后，经N-乙基-N-亚硝基脲预处理的胎鼠脑细胞在扁平上皮样细胞下层显示出神经细胞的局灶性增殖。神经细胞呈现出多种形式的众多背褶以及数量增加的其他表面微突起。在第40天至第100天之间，观察到双极和多极神经细胞结节，其表面微观结构复杂，包括许多泡状突起和褶边以及数量增加的微绒毛。100 - 210天后，增殖更快、形态改变的细胞形成“堆积”灶，导致整个表面出现大量长微绒毛、大褶边和泡状突起的均匀细胞群体。在首次观察到将细胞重新植入同基因宿主后具有致瘤性（约273天）之前，细胞一直保持相同的改变后的表面结构。因此，在细胞具有致瘤性之前100多天就可观察到肿瘤细胞特有的表面改变。
