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首页> 美国卫生研究院文献>Biochemical Journal >Characterization of difluoromethylornithine-resistant mouse and human tumour cell lines.
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Characterization of difluoromethylornithine-resistant mouse and human tumour cell lines.

机译：耐二氟甲基鸟氨酸的小鼠和人肿瘤细胞系的表征。

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摘要

Four mouse and two human tumour cell lines resistant to alpha-difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), were analysed for the activities of polyamine-biosynthetic and -biodegradative enzymes as well as for cellular polyamine contents. In all but one of these cell lines the resistance to DFMO was based on an overproduction of ODC. In a human myeloma cell line the resistance was based on a greatly enhanced arginase activity. Except for one L1210 variant cell line, all the resistant cell lines contained elevated S-adenosylmethionine decarboxylase activity. Similarly, all the resistant mouse, but not human, cell lines displayed enhanced spermidine and spermine synthase activities. Arginase activity was detected only in human cell lines. In both DFMO-resistant cell lines the activity of arginase was strikingly elevated. Of the biodegradative enzymes, polyamine oxidase activity was readily detectable in all mouse cells, but no measurable activity was found in the human cells. Spermidine/spermine N1-acetyltransferase activity was elevated in three out of four resistant mouse cell lines. Even though the concentration of spermidine was usually lower in the overproducer cells, this was compensated by an increased content of spermine. The two resistant human myeloma cells contained intracellular ornithine concentrations that were from more than 5 to more than 20 times higher than those in the parental cells.
机译：分析了对鸟氨酸脱羧酶（ODC）的不可逆抑制剂α-二氟甲基鸟氨酸（DFMO）有抵抗力的四种小鼠和两种人类肿瘤细胞系的多胺生物合成酶和生物降解酶活性以及细胞中多胺含量。在所有这些细胞系中，除其中一种以外，对DFMO的抵抗都是基于ODC的过量生产。在人类骨髓瘤细胞系中，抗性基于大大增强的精氨酸酶活性。除一种L1210变异细胞系外，所有耐药细胞系均具有升高的S-腺苷甲硫氨酸脱羧酶活性。类似地，所有抗性小鼠细胞系，而非人类细胞系均显示出增强的亚精胺和精胺合酶活性。仅在人细胞系中检测到精氨酸酶活性。在两种DFMO抗性细胞系中，精氨酸酶的活性都显着提高。在所有的生物降解酶中，多胺氧化酶的活性在所有小鼠细胞中均很容易检测到，但在人细胞中未发现可测量的活性。在四个耐药小鼠细胞系中的三个中，亚精胺/亚精胺N1-乙酰基转移酶活性升高。即使在生产过量的细胞中亚精胺的浓度通常较低，这也可以通过增加精胺的含量来补偿。两种抗性人类骨髓瘤细胞的细胞内鸟氨酸浓度比亲代细胞高5倍至20倍以上。

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