Hidaka K, Endo H, Akiyama S, Kuwano M
Cell. 1978 Jun;14(2):415-21. doi: 10.1016/0092-8674(78)90126-5.
Amphotericin B is a polyene macrolide antibiotic which interacts specifically with sterols in mammalian cell membranes. Amphotericin B-resistant (AMBr) lines of stable phenotype have been isolated from cultured Chinese hamster (V79) cells. Three AMBr clones (AMBr-1, -2 and -3) isolated independently after treatment with nitrosoguanidine were resistant to greater than or equal to microgram/ml of the antibiotic, while DNA synthesis as well as the colony-forming ability of the parental V79 cells was blocked by greater than 80% of control in the presence of 20--50 microgram/ml amphotericin B. The AMBr cell line also exhibited increased resistance to other polyene macrolide antibiotics such as nystatin and pentamycin. Other agents, however, such as cytosine arabinoside or ricin, blocked DNA synthesis in AMBr cells to the same extent as in V79 cells. The amphotericin B resistance phenotype was stably retained even after AMBr cells were cultured in the absence of the drug for over 200 generations. The control of free cholesterol or its esters was significantly decreased in all three resistant clones. Furthermore, cholesterol synthesis from acetate as well as mevalonate was partly defective in AMBr cells, compared with that in V79 cells.
两性霉素B是一种多烯大环内酯类抗生素，它能与哺乳动物细胞膜中的固醇特异性相互作用。已从培养的中国仓鼠（V79）细胞中分离出具有稳定表型的两性霉素B抗性（AMBr）细胞系。用亚硝基胍处理后独立分离出的三个AMBr克隆（AMBr-1、-2和-3）对大于或等于微克/毫升的该抗生素具有抗性，而在存在20 - 50微克/毫升两性霉素B的情况下，亲代V79细胞的DNA合成以及集落形成能力被抑制超过对照的80%。AMBr细胞系对其他多烯大环内酯类抗生素如制霉菌素和戊霉素也表现出增强的抗性。然而，其他试剂，如阿糖胞苷或蓖麻毒素，在AMBr细胞中阻断DNA合成的程度与在V79细胞中相同。即使在无药物的情况下将AMBr细胞培养超过200代后，两性霉素B抗性表型仍能稳定保留。在所有三个抗性克隆中，游离胆固醇或其酯的调控均显著降低。此外，与V79细胞相比，AMBr细胞中由乙酸盐以及甲羟戊酸合成胆固醇的过程存在部分缺陷。
