Relationship between glycolysis and proliferation of L 1210 cells in vitro: effect of a new pharmacological effector: RA-233.
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Biomedical subjects
Publications and source records attributed to B Desoize.
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Methotrexate, at non lethal doses, alters the glycolysis of leukaemic L 1210 cells. Glucose uptake and lactate excretion are increased but lactate/glucose ratio remains constant. The activity of glycolytic enzymes in the cytoplasm is increased and the level of intracellular ATP is greatly enhanced.
THC decreases 3H-thymidine uptake within 15 sec. after addition of the drug to the culture (L1210 murine lymphoma cells and human lymphocytes). Experiments performed at 0 degrees C indicate that THC has no action on thymidine binding to the carrier. THC in micromolar concentration inhibits DNA synthesis through a alteration of membrane configuration.
Methotrexate, in non-lethal doses, greatly enhances anaerobic glycolysis in L1210 cells. Lactate/glucose ratio remains constant but intracellular levels of glycolytic enzymes are increased. ATP accumulating in the cells seems to reflect an alteration of regulation of the glycolysis.
Imipramine, diazepam, chlordiazepoxide, and meprobamate inhibit incorporation of 3H-thymidine in human lymphocytes in culture. For the first three drugs, 50% inhibition occurs at a concentration of 5 X 10(-5) M, and for meprobamate at a concentration of 10(-3 M. Ethanol has no action up to 10(-1) M.
The lymphocyte response to phytohemagglutinin (PHA) as measured by [13H]thymidine incorporation is equally inhibited by 10(-5) to 10(-4) M concentrations of delta8, and delta9-tetrahydrocannabinol (THC), their 11-hydroxymetabolites, cannabidiol, cannabinol, cannabichromene, cannabicyclol. A similar inhibiting effect is produced by olivetol, which has the structure of the C ring common to all of these cannabinoids and their metabolites that accumulate in tissues. THC inhibits intracellular and intramolecular incorporation of thymidine, uridine, and leucine. This inhibition can be observed within 15 min after addition of THC to the culture medium. The cytotoxicity of THC is a function of the concentration of serum in the culture medium. The higher the concentration of serum, the more the cells are protected against the toxicity of THC. The cytotoxicity of THC is reversible by washing, after the cells have been incubated for 24 hr with the drug. Lymphocytes incubated with THC or olivetol present a significantly larger number of hypodiploid cells and a significant increase in segregational errors of chromosomes. The inhibitory effect of THC on macromolecular synthesis might be mediated by an alteration of the plasma membrane by the drug.
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