Selective protection against the cytotoxicity of methotrexate and methotrexate-poly(lysine) by thiamine pyrophosphate, heparin and leucovorin.

  title={Selective protection against the cytotoxicity of methotrexate and methotrexate-poly(lysine) by thiamine pyrophosphate, heparin and leucovorin.},
  author={Wei Shen and Hugues J.-P. Ryser},
  journal={Life sciences},
  volume={28 11},
Abstract The cytotoxicity of both methotrexate (MTX) and methotrexate-poly(L-lysine) conjugate (MTX-poly(lys)) on L929 mouse fibroblasts can be prevented by the simultaneous administration of Leucovorin. Thiamine pyrophosphate, an inhibitor for MTX-transport, protects cells from the toxicity of MTX, but not of MTX-poly(lys). Heparin at low concentration (1 μg/m1) completely abolishes the toxic effect of MTX-poly(lys), but not of MTX. These results suggest that although MTX and MTX-poly(lys… Expand
Interaction of methotrexate poly(L-lysine) with transformed hepatic cells in culture.
The role of poly( l -lysine) as a carrier was demonstrated, since methotrexate uptake was inhibited by folinic acid, which had no effect on the cells' uptake or hydrolysis of [ 3 H]methotrexate poly( d-lysine). Expand
Effect of liposomes sensitized with methotrexate-gamma-dimyristoylphosphatidylethanolamine on cells that are resistant to methotrexate.
The present experiments suggest that liposomes prepared with MTX-gamma-DMPE can partially reverse the methotrexate resistance of CEM/R1 cells that is due to overproduction of the target enzyme. Expand
Methotrexate conjugate with branched polypeptide influences Leishmania donovani infection in vitro and in experimental animals.
It is demonstrated that MTX conjugates in which the drug is covalently attached to carrier have pronounced leishmanicid activity, and the number of Leishmania donovani parasites in infected macrophages are markedly reduced in conjugate treated animals. Expand
Drug-Poly(Lysine) Conjugates: Their Potential for Chemotherapy and for the Study of Endocytosis
Poly(L-Lysine) (poly(Lys)), a strongly cationic macromolecule, is efficiently transported into cells by endocytosis (Ryser et al., 1982). This uptake is preceeded by a strong adsorption to the cellExpand
Targeting, internalization, and cytotoxicity of methotrexate-monoclonal anti-stage-specific embryonic antigen-1 antibody conjugates in cultured F-9 teratocarcinoma cells.
Results indicate that the MTX antibody conjugate binds specifically to F-9 cells, and is internalized and intracellularly degraded to release a small molecular active drug. Expand
Drug Delivery with Protein and Peptide Carriers
Drugs or toxins such as methotrexate, adriamycin, daunomycin, fluorodeoxyuridine, neocarzinostatin, and ricin can be bound, either covalently or by occlusion, to proteins, synthetic polypeptides, andExpand
Immunogenicity of poly-D-lysine, a potential polymeric drug carrier
Abstract The antibody response against poly-D-lysine, a potential polymeric drug carrier, was evaluated in rabbits. Intradermal injection of poly-D-lysine in rabbits induced the formation ofExpand
Binding sites and endocytosis of heparin and polylysine are changed when the two molecules are given as a complex to Chinese hamster ovary cells.
The polylysine X heparin complex is characterized as a potential carrier for intracellular drug delivery through endocytosis and the interaction of this complex with the surface of Chinese hamster ovary cells is investigated. Expand


Poly (L-lysine) and poly (D-lysine) conjugates of methotrexate: different inhibitory effect on drug resistant cells.
Conjugation of methotrexate to poly(L-lysine) markedly increases its cellular uptake and offers a new way to overcome drug resistance related to deficient transport and to give rise in the cell to a pharmacologically active breakdown product. Expand
Photoinactivation of the methotrexate transport system of L1210 cells by 8-azidoadenosin 5'-monophosphate.
It is shown that complete photoinactivation of methotrexate transport could not be obtained from a single exposure to 8-azido-AMP, but it could be achieved by the repetitive illumination of cells in a fresh medium and the phosphate and folate/adenine transport systems of L1210 cells are not affected by irradiation in the presence of 7-azidoadenosine-AMP. Expand
Binding properties of the 5-methyltetrahydrofolate/methotrexate transport system in L1210 cells.
The measured binding activity does not represent low-temperature transport of substrate into cells, since it is readily saturable with time and is eliminated by either washing the cells with buffer or by the addition of excess unlabeled substrate. Expand
Site of action of a polyanion inhibitor of phagosome-lysosome fusion in cultured macrophages.
This semi-synthetic compound chlorite-oxidized amylose (COAM) prepared fromAmylose starch differs from previously reported inhibitors by its rapidity in suppressing P-LF, and shows low toxicity and a wide range of effective dose. Expand
Inhibitory effect of polycations on the transplantability of mouse leukaemia reversed by heparin.
L'incubation avec la polyornithine et le Dextran-DEAE, pendant une heure, provoquait une inhibition complete de the transplantabilite, chez 70 a 85% des animaux, and augmentait, de facon significative, the survie des animau restants. Expand