A new method for delivering alkanes to mammalian cells: preparation and preliminary characterization of an inclusion complex between beta-cyclodextrin and pristane (2,6,10,14-tetramethylpentadecane).
Pristane (2,6,10,14-tetramethylpentadecane) is an isoalkane which induces plasma cell tumorigenesis in genetically susceptible strains of mice. Attempts to study the biological activity of pristane on cells in vitro have been hindered by the extreme hydrophobicity and hence complete immiscibility of the compound in aqueous cell culture media. In comparing different solubilization protocols such as using organic solvents, liposomes, and molecular encapsulation into beta-cyclodextrin (beta-CyD), it was found that beta-CyD/pristane inclusion complexes were optimal for delivery of the hydrocarbon to cells. After solubilization in beta-CyD, pristane was cytotoxic (51Cr release assay) to murine B lymphocyte lines in culture (P388, NSF-1, and SJL-4) and inhibited the lipopolysaccharide-induced stimulation of splenic B lymphocyte proliferation and blast formation (Coulter counter analysis) when added in the micromolar concentration range. Moreover, sub-toxic concentrations of beta-CyD/pristane inclusion complexes were found to have a small but reproducible mitogenic effect [( 3H]thymidine incorporation) on SJL-4 and 308 (murine initiated keratinocyte) cells in culture but not on P388 cells. The results indicate that molecular encapsulation of pristane into beta-CyD provides a new and effective method for delivering low concentrations of alkanes to mammalian cells in vitro.
Janz
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Laboratory of Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
Shacter
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E
D000473:Alkanes / Q000737:chemistry* / Q000633:toxicity; D000818:Animals; D001402:B-Lymphocytes / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002860:Chromium Radioisotopes; D003505:Cyclodextrins / Q000737:chemistry*; D008081:Liposomes; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D012995:Solubility; D013729:Terpenes / Q000737:chemistry* / Q000633:toxicity; D013936:Thymidine; D014316:Tritium; D014407:Tumor Cells, Cultured; D047392:beta-Cyclodextrins
D000473:Alkanes; D002860:Chromium Radioisotopes; D003505:Cyclodextrins; D008081:Liposomes; D013729:Terpenes; D047392:beta-Cyclodextrins; D014316:Tritium; C009042:pristane; C031215:betadex; D013936:Thymidine