Abstract

The influences of two naturally occurring psychoactive cannabinoids (Δ 9-tetrahydrocannabinol and Δ 8-tetrahydrocannabinol), of a psychoactive cannabinoid metabolite (11-OH-Δ 9-THC) and of a nonpsychoactive cannabinoid (cannabinol) on the composition, metabolism and structure of human (HeLa cell) chromatin were examined. The effects of all four cannabinoids on the composition and synthesis of chromosomal proteins were studied by pulse-labeling with [ 3H]leucine. The relative amounts of both histones and nonhistone chromosomal proteins remained unaffected, but a decrease in [ 3H]leucine incorporation into both histones and nonhistone proteins was observed. Post-translational acetylation and phosphorylation of chromosomal proteins were studied in cannabinoid-treated cells by pulse-labeling with [ 3H]acetate and [ 32P], Variations were observed in [ 3H]acetate incorporation into histones and [ 32P] incorporation into both histones and nonhistone chromosomal proteins. Pancreatic DNase I digestion of chromatin from cannabinoid-treated HeLa cells failed to demonstrate any drug-induced alteration in DNA-protein interactions.

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