ENTRY OF LETHAL DOSES OF ABRIN, RICIN AND MODECCIN INTO THE CYTOSOL OF HELA-CELLS

ENTRY OF LETHAL DOSES OF ABRIN, RICIN AND MODECCIN INTO THE CYTOSOL OF HELA-CELLS
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DOI:
10.1016/0014-4827(80)90270-0
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发表时间:
1980-01-01
影响因子:
3.7
通讯作者:
PIHL, A
PIHL, A
中科院分区:
医学3区
文献类型:
--
作者:
EIKLID, K;OLSNES, S;PIHL, A

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为了评估胞浆中需要多少个有毒凝集素分子才能杀死HeLa细胞,研究了这些毒素对蛋白质合成和培养效率的影响。细胞暴露于毒素1h后的孵育时间对蛋白质合成的抑制程度有很大影响。全部毒性效应在暴露后20h左右表现出来。在进一步孵育时,蛋白质合成再次以与对照细胞相当的速度增加。暴露于浓度增加的毒素后,20h后细胞蛋白质合成的抑制与培养效率的抑制表现出很好的一致性,表明蛋白质合成的抑制可以作为细胞杀伤的一种衡量标准。毒素对蛋白质合成的抑制遵循一级动力学,表明细胞被全效应或无效应所杀死。放射自显影研究表明,在暴露于中等浓度的毒素后,一些细胞的蛋白质合成完全消失,而其余细胞的蛋白质合成似乎以正常速度进行。结果表明,阿贝林、蓖麻毒素或莫德霉素的一个分子进入胞浆对HeLa细胞是致命的,并且毒素进入细胞质的效率与整体毒素摄取速率相比非常低。
In attempts to assess how many molecules of the toxic lectins abrin, ricin and modeccin are needed in the cytosol to kill HeLa cells the effect of these toxins on protein synthesis and plating efficiency was studied. The incubation time of the cells after a 1 h exposure to the toxins influenced strongly the extent of inhibition of protein synthesis. The full toxic effect was expressed about 20 h of incubation after the exposure. On further incubation, protein synthesis again increased at a rate comparable to that in the control cells. After exposure to increasing concentrations of toxins the inhibition of cellular protein synthesis measured after 20 h showed excellent agreement with the inhibition of plating efficiency, indicating that the inhibition of protein synthesis can be used as a measure of cell killing. The inhibition of protein synthesis by toxins was found to follow first order kinetics, indicating that the cells are killed by an all- or none-effect. Autoradiographic studies indicated that after exposure to intermediate toxin concentrations protein synthesis was completely abolished in some cells, whereas it appeared to proceed at a normal rate in the remaining cells. The results provide evidence that penetration of one molecule of abrin, ricin or modeccin into cytosol is lethal to HeLa cells and that the efficiency of toxin entry into the cytoplasm is very low compared to the rate of bulk toxin uptake.