title: Biochemical parameters of resistance of an adriamycin-resistant subline of P388 leukemia to emetine, an inhibitor of protein synthesis.
abstract: The effects of emetine on protein and DNA synthesis in vitro and in vivo were compared in P388 leukemia cells (P388/S) and in an adriamycin-resistant subline of P388 leukemia (P388/ADR), which was completely cross-resistant in vivo to emetine. In P388/ADR cells in vitro no apparent resistance to emetine was found; no difference in cytotoxicity was evident in P388/S or P388/ADR cells exposed to emetine in vitro for 1 or 6 hours. Protein and DNA synthesis was inhibited to a similar extent in P388/S and P388/ADR cells at equivalent concentrations of the drug. However, inhibition of protein synthesis by emetine in P388/ADR cells was more reversible than in P388/S cells when the cells were exposed to emetine and subsequently incubated in drug-free medium for 1 hour prior to addition of labeled L-leucine. Differences between P388/S and P388/ADR cells were evident in vivo. The duration of inhibition (greater than 90%) of protein and DNA synthesis in P388/ADR cells was about 8 hours compared to 24 hours in P388/S cells following administration of a therapeutic dose of 25 mg emetine/kg to tumor-bearing mice. The level of radioactivity in the P388/ADR cells 24 hours after in vivo administration of the emetine analog, (+/-)-[3'-14C]2,3-dehydroemetine, was only 26% of that in P388/S cells. This evidence suggests that the resistance of P388/ADR to emetine is due to decreased retention of the drug.
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004273:DNA, Neoplasm / Q000096:biosynthesis; D004317:Doxorubicin / Q000494:pharmacology*; D004351:Drug Resistance; D004640:Emetine / Q000008:administration & dosage / Q000494:pharmacology*; D007942:Leukemia, Experimental / Q000188:drug therapy / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D013997:Time Factors
chemical_list: D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D004317:Doxorubicin; D004640:Emetine