Isolation of methylcholanthrene-"initiated" C3H/10T1/2 cells by inhibiting neoplastic progression with retinyl acetate.
Isolation of methylcholanthrene-"initiated" C3H/10T1/2 cells by inhibiting neoplastic progression with retinyl acetate.
复制标题
通过用乙酸视黄酯抑制肿瘤进展来分离甲基胆蒽“启动”C3H/10T1/2 细胞。
DOI：
10.1093/carcin/3.3.279
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发表时间：
1982
期刊：
影响因子：
4.7
通讯作者：
J. Bertram
中科院分区：
文献类型：
--
作者：
L. Mordan;L. Bergin;J. E. Budnick;R. R. Meegan;J. Bertram
经3-甲基胆蒽处理的10T1/2细胞克隆具有“起始”细胞的基本特征。在醋酸视黄酯存在下，该克隆表现出接触抑制生长控制，在形态上与亲本10T1/2细胞系难以区分。体外去除视黄醇醋酸酯会在3周潜伏期后导致肿瘤转化。通过共培养正常和“启动”的10T1/2细胞，重建经典的10T1/2转化体系，在潜伏期为3-4周后形成II型或III型灶，另外22%形成I型灶。用肿瘤启动子12- o - tetradecanoylphorol -13-acetate处理“启动”的10T/2细胞，通过将潜伏期缩短至3周以下，加速了共培养系统中转化灶的形成。将10(6)个“初始化”细胞/小鼠s.c.注射到裸鼠体内，经过5-7周的潜伏期后，出现了逐渐生长的纤维肉瘤。膳食中补充4-羟基苯基视黄酰胺可防止肿瘤形成；停药后6周，所有存活小鼠均出现肿瘤。我们相信这个细胞系具有“初始化”细胞的所有特征。有了这个新的细胞系，命名为INIT/10T1/2，我们现在可以研究导致肿瘤转化的生长控制机制的早期生化变化以及维生素A化学预防癌症的机制。
A clone of 3-methylcholanthrene-treated 10T1/2 cells has been isolated which possesses basic characteristics expected of "initiated" cells. In the presence of retinyl acetate, this clone exhibits contact inhibited growth control and is morphologically indistinguishable from the parental 10T1/2 cell line. Removal of retinyl acetate in vitro results in neoplastic transformation after a latent period of 3 weeks. The classical 10T1/2 transformation system was reconstructed by coculturing normal and "initiated" 10T1/2 cells formed either Type II or Type III foci after a latent period of 3-4 weeks, and an additional 22% formed Type I foci. Treatment of "initiated" 10T/2 cells with the tumor promoter 12-O-tetradecanoylphorbol-13-acetate accelerated the formation of transformed foci in the coculture system by reducing the length of the latent period to less than 3 weeks. Injection of 10(6) "initiated" cells/mouse s.c. into nude mice resulted in the appearance of progressively growing fibrosarcomas after a latent period of 5-7 weeks. Dietary supplementation with 4-hydroxyphenyl-retinamide prevented tumor formation; after drug withdrawal, tumors developed in all surviving mice after 6 weeks. We believe this cell line possesses all characteristics expected of "initiated" cells. With this new cell line, designated INIT/10T1/2, we can now study the early biochemical changes in growth control mechanisms resulting in neoplastic transformation and the mechanism(s) of chemoprevention of cancer by vitamin A.