Some biochemical properties of Chinese hamster cells sensitive and resistant to actinomycin D.
A graded series of drug-resistant Chinese hamster sublines has been examined for biochemical changes accompanying resistance to actinomycin D. The most highly resistant subline, DC-3F/AD X, is maintained at 10 microg/ml of the antibiotic. It was shown that over 250 times more actinomycin D is required to inhibit RNA synthesis in this subline than in the parental DC-3F line. The DC-3F/AD X subline was also shown to have a somewhat reduced capacity to transport uridine as compared to parental cells. Sensitive cells took up over 50 times more tritiated antibiotic than the most resistant cells, as determined in a 1-h assay. Uptake of actinomycin D was shown to be temperature-dependent in both resistant and sensitive cells and was not influenced by various metabolic inhibitors. Resistance could not be explained by a rapid uptake and release of the antibiotic, as demonstrated in efflux experiments, or by its metabolism. In addition, highly resistant cells which are cross-resistant to puromycin were shown to have a reduced capacity to take up labeled puromycin. These studies provide further evidence indicating that the mechanism of resistance to actinomycin D is reduced permeability to drug and suggesting that cell membrane alteration accounts for resistance to both actinomycin D and puromycin.
D000818:Animals; D002478:Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006224:Cricetinae; D003609:Dactinomycin / Q000378:metabolism / Q000494:pharmacology*; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D004351:Drug Resistance; D011136:Polysorbates / Q000494:pharmacology; D011691:Puromycin / Q000494:pharmacology; D012313:RNA / Q000096:biosynthesis; D013696:Temperature; D013936:Thymidine / Q000378:metabolism; D013997:Time Factors; D014316:Tritium; D014529:Uridine / Q000378:metabolism
D011136:Polysorbates; D014316:Tritium; D003609:Dactinomycin; D011691:Puromycin; D012313:RNA; D013936:Thymidine; D014529:Uridine