Abstract
(-)-Δ9-tetrahydrocannabinol (Δ9THC) was found to be a noncompetitive inhibitor for the uptake of thymidine into TCA soluble material by Reuber H-35 hepatoma cells. It also reduced uptake rates of adenosine, guanosine and cytidine. A 50% inhibition of thymidine uptake was produced with Δ9THC concentrations of 70 µM while cytidine uptake was inhibited to the same extent at 30 µM Δ9THC. The drug had no significant effect on the uptake of uridine, leucine and proline. Intracellular thymidine-containing nucleotide pools, isolated by thin layer chromatography after pulse labeling of the Δ9THC treated cells with 3H thymidine, were significantly diminished. Concentrations of 70 µM Δ9THC reduced radioactive dTMP, dTDP and dTTP levels to 50% of those of the control cells. As thymidine kinase activity was not inhibited by Δ9THC, it is concluded that Δ9THC inhibits thymidine uptake at some step prior to formation of dTMP.
ACKNOWLEDGMENTS We thank Professor L. S. Harris, Department of Pharmacology, Medical College of Virginia for his gift of the Δ9THC, Mrs. Esther Torres for clerical help and Mr. Juan Coloca for the photographic work.
- Copyright © 1979 by Academic Press, Inc.
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