Effect of 5-fluorouracil and thymidine on the transmembrane potential and zeta potential of HeLa cells.

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.