Differential Control of Synergistic Effect with Polyene Macrolide Antibiotics upon Chinese Hamster Cells in Vitro¹

An amphotericin B-resistant cell (AMB^R-1), which was isolated from aneuploid Chinese hamster cells (V79), was found to show much higher resistance than its parent V79 cells to other polyene antibiotics, such as pentamycin and filipin. To obtain the 50 to 60% inhibition of the control protein synthesis activity by a synergistic combination of fusidic acid and amphotericin B, 50 µg fusidic acid per ml were combined with 10 µg amphotericin B in V79 cells, whereas in AMB^R cells 50 µg fusidic acid per ml were combined with 100 µg polyene antibiotic per ml. Bleomycin (10 µg/ml), which alone did not affect cellular DNA synthesis, inhibited DNA synthesis of V79 cells by more than 90% of the control activity when combined with only 1 µg pentamycin per ml, whereas a similar extent of inhibition in AMB^R cells was observed by combination with more than 5 µg pentamycin per ml.