Brajtburg J, Elberg S, Medoff J, Kobayashi G S, Schlessinger D, Medoff G
Antimicrob Agents Chemother. 1984 Dec;26(6):892-7. doi: 10.1128/AAC.26.6.892.
High concentrations of amphotericin B (AmB) killed mouse L cells, but low concentrations increased plating efficiency and stimulated the incorporation of labeled precursors into DNA and RNA. Thus, there were two disparate effects of AmB on L cells, stimulatory and toxic, and they occurred in distinct dose-related stages. AmB also affected the permeability of L cells. In dose-response studies, increases in cell membrane permeability, measured as the loss of K+ ions, occurred along with the stimulation of [3H]uridine incorporation into RNA. In contrast, stimulation of [3H]thymidine incorporation into DNA was only observed in cells recuperating from AmB-induced permeability changes. When the K+ concentration in the medium was lowered to 0.5 from 4.5 mM, or when 1 mM ouabain was added to the cultures, cell killing was potentiated, but the stimulatory and permeabilizing effects of subtoxic concentrations of AmB were unaffected. Furthermore, etruscomycin, a polyene antibiotic without any permeabilizing effects, nevertheless induced an enhancement of plating efficiency and of incorporation of [3H]uridine into RNA and [3H]thymidine into DNA. Our results suggest that the dose-related stimulatory, permeabilizing, and toxic effects of AmB most probably have distinct mechanisms of action and may be independent of one another.
高浓度的两性霉素B（AmB）可杀死小鼠L细胞，但低浓度时可提高接种效率，并刺激标记前体掺入DNA和RNA。因此，AmB对L细胞有两种不同的作用，即刺激作用和毒性作用，且它们发生在不同的剂量相关阶段。AmB还影响L细胞的通透性。在剂量反应研究中，细胞膜通透性的增加（以钾离子的流失来衡量）与[3H]尿苷掺入RNA的刺激作用同时出现。相反，只有在从AmB诱导的通透性变化中恢复的细胞中才观察到[3H]胸苷掺入DNA的刺激作用。当培养基中的钾离子浓度从4.5 mM降至0.5 mM时，或者当向培养物中加入1 mM哇巴因时，细胞杀伤作用增强，但亚毒性浓度的AmB的刺激作用和通透作用不受影响。此外，伊曲康唑，一种没有任何通透作用的多烯抗生素，却能提高接种效率，并促进[3H]尿苷掺入RNA以及[3H]胸苷掺入DNA。我们的结果表明，AmB与剂量相关的刺激、通透和毒性作用很可能具有不同的作用机制，并且可能彼此独立。
