Influence of Δ9-tetrahydrocannabinol on cell proliferation and macromolecular biosynthesis in human cells

Abstract

To elucidate the influence of Δ 9-tetrahydrocannabinol ( Δ 9-THC) on proliferation of human cells and macromolecular biosynthetic events associated with the proliferative process, we have examined the following parameters of Δ 9-THC-treated HeLa S 3 cells grown in suspension culture: (1) exponential population growth, (2) subcellular localization of the drug, (3) protein, DNA and RNA synthesis, (4) composition and metabolism of chromosomal proteins, and (5) chromatin transcription in vitro. Exponentially growing HeLa S 3 cells exhibit a dose-dependent depression in proliferative activity when exposed to concentrations of Δ 9-THC ranging from 5 to 40 μM. Approximately 9 per cent of the compound added to suspension cultures went into the cells, and of this, approximately 99 per cent was recovered from the cytoplasmic fraction and approximately 1 per cent from the nuclear fraction. The total cellular amount of Δ 9-THC was calculated to be 1.44 ng/10 3 cells. Treatment of cells with 10–40 μM Δ 9-THC resulted in a dose-dependent decrease in the apparent synthesis of DNA and RNA as well as in the sizes of the radiolabeled intracellular acid-soluble nucleotide precursor pool. Similar results were observed in the protein-synthesizing ability of cells treated with 30–40 μM concentrations of Δ 9-THC. Template activity in vitro of chromatin was not affected by treatment of the cells with 10–30 μM concentrations of the drug. Polyaclylamide gel electrophoretic analysis of chromosomal proteins pulse labeled with [ 3H] l-leucine suggests that Δ 9-THC does not affect the composition, the rates of synthesis, or the turnover of histones and nonhistone chromosomal proteins.