PLASMA-MEMBRANE INHIBITION OF MACROMOLECULAR PRECURSOR TRANSPORT BY THC

10-6 to 10-4 M .DELTA.-9-tetrahydrocannabinol (THC) or of other cannabinoids, which have in common the C ring of olivetol, inhibit [3H]thymidine incorporation in cultured human lymphocytes. The inhibitory effect of olivetol derivatives is related to their octanol-H2O partition coefficient (liposolubility). Within 15 min of incubation THC inhibits precursor pool formation and macromolecular incorporation of thymidine, uridine and Leu. THC inhibits [14C]aminoisobutyric acid uptake into the cell but does not alter the cellular leakage of this amino acid analog. Using the isotopic dilution technique with L1210 murine lymphoma cells and human lymphocytes, THC decreases [3H]thymidine uptake within 15 s after addition of the drug to the culture. Experiments performed at 0.degree. C indicate that THC has no action on thymidine binding to the carrier. Apparently THC in micromolar concentration inhibits DNA synthesis through a non-specific change in membrane configuration. This effect, due to the liposolubility of the drug, could induce conformational changes of membrane-bound transport systems which would inhibit their function.