Control of permeation of bleomycin A2 by polyene antibiotics in cultured Chinese hamster cells.
Control of permeation of bleomycin A2, a well-known antitumor antibiotic, in combination with various polyene macrolide antibiotics was analyzed in cultured Chinese hamster cells in vitro. Three polyene antibiotics, filipin, pentamycin, and pimaricin, were found to enhance the action of bleomycin A2 remarkably, while amphotericin B or nystatin could not. Although DNA synthesis and colony-forming activity of polyene-sensitive Chinese hamster V79 cells were synergistically inhibited by the combination of filipin and bleomycin A2, in a polyene-resistant subline (AMBR-1) derived from V79, they were only slightly affected in the presence of both drugs. The cellular uptake of [14C]bleomycin A2 by V79 was enhanced 2- to 4-fold in the presence of increasing doses of filipin or pentamycin, but not in the presence of amphotericin B. The treatment of V79 cells with filipin for 20 to 30 min was enought to block DNA synthesis almost completely when combined with 20 microgram belomycin A2 per ml. The pretreatment of the hamster cells with 6 microgram filipin per ml for 60 min continued to enhance the inhibitory action by bleomycin A2 of DNA synthesis up to 5 hr after the removal of filipin from the cultured medium.
D000666:Amphotericin B / Q000494:pharmacology; D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D001761:Bleomycin / Q000378:metabolism* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002999:Clone Cells / Q000187:drug effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000096:biosynthesis; D004357:Drug Synergism; D005372:Filipin / Q000494:pharmacology; D018942:Macrolides; D010866:Natamycin / Q000494:pharmacology; D009761:Nystatin / Q000494:pharmacology; D011090:Polyenes / Q000494:pharmacology
D000935:Antifungal Agents; D018942:Macrolides; D011090:Polyenes; D001761:Bleomycin; D009761:Nystatin; C011827:fungichromin; D000666:Amphotericin B; D005372:Filipin; D010866:Natamycin; D004247:DNA