Chromosome breakage in users of marihuana

Δ⁹-Tetrahydrocannabinol (THC) elicited a dose-dependent (3.2–24 μM) response for form/movement, cellular growth and division in log growth phase and division-synchronized Tetrahymena pyriformis GL. Progressive dose-dependent action of THC on division delays in division-synchronized cell cultures was correlated with a concomitant reduction of division maxima and the percent of cells that completed division I. THC depressed the incorporation of 5-³H-uridine, 2-¹⁴C-thymidine and L-3-¹⁴C-phenylalanine into RNA, DNA and protein macromolecules respectively of division-synchronized Tetrahymena during division I, The depression of incorporation of 5-³H-uridine into nucleic acid macromolecules was correlated with a reduction of exogeneous precursor in the cellular pool. The specific activity of radiolabeled mRNA and nascent polypeptides of polyribosomal fractions from synchronized cells was reduced by THC treatment. THC caused an inhibition of the incorporation of 5-³H-uridine into ribosomal RNA (17S and 25S RNA) and ribosomal precursor RNA (35S RNA) of synchronized cells.

Section: Discussionmentioning

confidence: 98%

Action of Δ9-Tetrahydrocannabinol on Cell Division and Macromolecular Synthesis in Division-Synchronized Protozoa

McClean

Zimmerman

1976

“…The authors also reported A'-THC was the only cannabinoid to inhibit in vitro DNA synthesis of Lewis lung cells and to inhibit in vivo growth of Lewis lung tumor while depressing DNA synthesis in bone marrow cells to a lesser extent. Chromosome aberrations in chronic marihuana smokers (23) and protrusions of heterochromatin from the nucleus (a drumstick appearance of chromatin) in the peripheral blood cells of chronic marihuana users (21) suggest that THC may influence DNA replication and repair. However, there is still strong doubt concerning the direct action of THC on DNA.…”

Section: Discussionmentioning

confidence: 99%

Δ1-Tetrahydrocannabinol, Cannabidiol and Cannabinol Effects on the Immune Response of Mice

Zimmerman¹,

Zimmerman²,

Cameron³

et al. 1977

△¹-Tetrahydrocannabinol (THC) elicited a dose-dependent (1, 5, 10 mg/kg) depression of the immune response, of immature mice, stimulated with sheep red blood cells. The impairment of humoral immunity was specific for THC but not for cannabidiol at 25 mg/kg or cannabinol at 25 mg/kg. The mice were given four daily doses (i.p.) of either drug or vehicle (Tween 80-propylene glycol in 1 % saline) or a single injection (i.p.) of sheep red blood cells in addition to four daily doses (i.p.) of drug or vehicle. Suppression of the antigenic response by THC was reflected as a reduction of splenic weight, reduction in the number of splenic antibody-forming cells, lowered hemagglutination titer and reduction in the percentage of splenic white pulp to total spleen volume.

“…In chronic marihuana smokers there are re ports of chromosome aberrations (31) and pro trusions of heterochromatin from the nuclei of peripheral blood cells (30), however, other studies (24) show no increase in chromosome aberrations in leukocytes obtained from indi-viduals given oral doses of marihuana extract or A9-THC.…”

mentioning

confidence: 99%

Nonmutagenic Action of Cannabinoids in vitro

Zimmerman¹,

Stich²,

San³

1978

Under the specific conditions reported for the separate tests Δ⁹-tetrahydrocannabinol (THC) did not elicit a mutagenic response in microbial and eukaryotic in vitro test systems. THC treatment to histidine auxotrophs of Salmonella typhimurium strains TA 98 (susceptible to frame shift mutation) and TA 100 (susceptible to base pair substitution) were investigated. Analysis for possible revertance in the presence and absence of S9 microsomal activation system indicated an absence of induction of gene mutation. Cultured fibroblasts from healthy individuals and DNA repair deficient Xeroderma pigmentosum patients display similar survival activity upon exposure to THC. There was no observable increase in the number of chromosome breaks or chromatid exchanges following exposure to THC or THC plus S9 microsomal fraction. THC, 11-OHΔ⁹-THC, cannabinol, and cannabidiol did not induce unscheduled DNA repair synthesis in cultured human fibroblasts. Moreover, THC did not suppress UV-induced DNA repair synthesis.