Walliser S, Redmann K
Cancer Res. 1978 Oct;38(10):3555-9.
The main result of the experiments reported in this paper is the observation that HeLa cells, when treated with 5-fluorouracil (5-FU), show a damped oscillatory response in the transmembrane potential. This effect is counteracted by thymidine. Damped oscillation in the transmembrane potential occurs within the first hr after addition of 5-FU, commencing with an initial hypopolarization. At low concentrations (10(-8) through 10(-7) M), hyperpolarization of the cell membrane is observed after lengthy incubation time (24 to 96 hr). Membrane depolarization is enhanced at higher concentrations (10(-6) through 10(-4) M) and with increasing exposure to the cytostatic substance. The surface charge or zeta potential of HeLa cells is altered to a lesser extent by 5-FU than is the transmembrane potential. Distinct effects can be observed as late as after 72 and 96 hr. When thymidine (2 x 10(-5) M) is added along with 5-FU, the depolarizing action of the antimetabolite can be abolished. Thymidine itself, at the concentration used, causes almost no change in membrane polarization. The results suggest that the effect of 5-FU on the cell membrane is related to the influence of the antimetabolite on cell growth. Moreover, this membrane effect might be the primary cause for the cytostatic action.
本文报道的实验主要结果是观察到，用5-氟尿嘧啶（5-FU）处理的HeLa细胞跨膜电位呈现衰减振荡响应。这种效应可被胸腺嘧啶核苷抵消。跨膜电位的衰减振荡在加入5-FU后的第一小时内出现，始于初始的去极化。在低浓度（10^(-8)至10^(-7) M）时，长时间孵育（24至96小时）后可观察到细胞膜超极化。在较高浓度（10^(-6)至10^(-4) M）以及增加与细胞生长抑制剂的接触时间时，膜去极化增强。5-FU对HeLa细胞表面电荷或ζ电位的改变程度小于对跨膜电位的改变。甚至在72小时和96小时后仍可观察到明显的效应。当胸腺嘧啶核苷（2×10^(-5) M）与5-FU一起添加时，抗代谢物的去极化作用可被消除。在所使用的浓度下，胸腺嘧啶核苷本身几乎不会引起膜极化的变化。结果表明，5-FU对细胞膜的作用与抗代谢物对细胞生长的影响有关。此外，这种膜效应可能是细胞生长抑制作用的主要原因。
