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佛波酯在体外促进致癌物暴露的非人灵长类动物细胞的生长和转化。

Phorbol ester promotes growth and transformation of carcinogen-exposed nonhuman primate cells in vitro.

作者信息

Marczynska B, Khoobyarian N, Chao T S, Tao M

机构信息

Department of Microbiology and Immunology, University of Illinois, College of Medicine, Chicago 60612.

出版信息

Anticancer Res. 1991 Sep-Oct;11(5):1711-7.

PMID:1768041
Abstract

Kidney cells established in vitro from a white-lipped marmoset (106) were exposed to N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) alone or in combination with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Low (0.1 micrograms/ml, 4 times), intermediate (1 microgram/ml) and high (1 microgram/ml, 4 times) doses of MNNG resulted in 100%, 50% and 2.8% of cell survival, respectively. High and low doses of MNNG had no effect on cell transformation. Upon exposure of cells to an intermediate dose of MNNG, 106 cells ecquired immortality and evolved into permanent cell line, 106-1M. However, the cells retained normal morphology and anchorage dependence. Chronic applications of TPA (0.1 micrograms/ml, 13 times) promoted 106-1M cells to morphological transformation and anchorage-independent growth but not to tumorigenicity in nude mice (106-1MT cell line). Chromosome analysis revealed only numerical changes in 106 cells and both numerical and structural aberrations in transformed 106-1MT cells. These changes in marmoset cells usually reflected cell culture instability leading to either senescence or to longer survival of cells in vitro. Chronic treatment with TPA did not result in downregulation of protein kinase C (PKC) in transformed 106-1MT cells. Instead, an additional species of PKC appeared in these cells.

摘要

从白唇狨猴(106)体外培养建立的肾细胞,单独或与12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯(TPA)联合暴露于N - 甲基 - N' - 硝基 - N - 亚硝基胍(MNNG)。低剂量(0.1微克/毫升,4次)、中等剂量(1微克/毫升)和高剂量(1微克/毫升,4次)的MNNG分别导致100%、50%和2.8%的细胞存活。高剂量和低剂量的MNNG对细胞转化没有影响。当细胞暴露于中等剂量的MNNG时,106细胞获得永生并演变成永久细胞系106 - 1M。然而,这些细胞保持正常形态并依赖贴壁生长。长期应用TPA(0.1微克/毫升,13次)促进106 - 1M细胞发生形态转化和不依赖贴壁生长,但在裸鼠中不具有致瘤性(106 - 1MT细胞系)。染色体分析显示106细胞仅存在数量变化,而转化的106 - 1MT细胞既有数量变化又有结构畸变。狨猴细胞的这些变化通常反映了细胞培养的不稳定性,导致细胞衰老或在体外存活时间延长。长期用TPA处理并未导致转化的106 - 1MT细胞中蛋白激酶C(PKC)下调。相反,这些细胞中出现了一种额外的PKC种类。

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