Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens.
Neoplastic transformation of human diploid fibroblast cells by chemical carcinogens.
复制标题
化学致癌剂对人二倍体成纤维细胞的肿瘤转化。
DOI：
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发表时间：
1978
影响因子：
11.1
通讯作者：
T. Kakunaga
中科院分区：
文献类型：
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作者：
T. Kakunaga
从正常成人皮肤活检样本中提取的培养成纤维细胞暴露于强致癌物4-硝基喹啉1-氧化物中。在氧化硝基喹啉处理后的连续传代培养中，一些细胞的生长模式发生了改变，如细胞密度增大和细胞堆积。形态学改变的细胞保留了这种生长模式，并成为转化细胞的建立细胞系，而在培养中没有表现出正常细胞有限的寿命特征。转化的细胞显示出更高的饱和密度和在软琼脂中生长的能力，这些特性通常与培养中细胞的肿瘤转化有关。选择先前存在的转化人类细胞作为这种观察到的转化的机制似乎不太可能，因为这些正常细胞的克隆也可以用来评估硝基喹啉氧化物的转化效果。初步结果表明，在硝基喹啉氧化处理后，这些人细胞的转化需要大量的细胞分裂。将转化后的细胞系皮下注射到裸小鼠（胸腺）体内，在接种部位产生实体瘤。用n -甲基-n '-硝基-n -亚硝基胍处理也能诱导细胞转化，其方式与用氧化硝基喹啉处理类似。然而，(i) 4-氨基喹啉1-氧化物（4-硝基喹啉1-氧化物的非致癌衍生物），（ii） 3-甲基胆蒽（一种不能被所使用的靶细胞代谢激活的致癌物）或（iii）溶剂二甲基亚砜都不能诱导转化。
Cultured fibroblast cells derived from a skin biopsy sample taken from normal human adult were exposed to a potent carcinogen, 4-nitroquinoline 1-oxide. Alterations of cell growth pattern such as higher density and piling up of cells were noticed in some fractions of cultures that were successively subcultured after nitroquinoline oxide treatment. Morphologically altered cells retained this growth pattern and became established lines of transformed cells without showing the limited life-span characteristic of normal cells in culture. The transformed cells showed a higher saturation density and the ability to grow in soft agar, properties that are usually correlated with neoplastic transformation of cells in culture. Selection of preexisting transformed human cells as a mechanism of this observed transformation seemed unlikely because clones of these normal cells could also be used to assess the transforming effect of nitroquinoline oxide. Preliminary results suggest that numerous cell divisions were required for the development of the transformation after nitroquinoline oxide treatment of these human cells. When the transformed cell lines were injected subcutaneously into nude (athymic) mice, solid tumors were produced at the site of inoculation. Treatment with N-methyl-N'-nitro-N-nitrosoguanidine also induced cell transformation, in a manner similar to treatment with nitroquinoline oxide. However, transformation was not induced with (i) 4-aminoquinoline 1-oxide (a noncarcinogenic derivative of 4-nitroquinoline 1-oxide), (ii) 3-methylcholanthrene (a carcinogen that cannot be metabolically activated by the target cells employed), or (iii) the solvent dimethyl sulfoxide.