Cannabinoids induce incomplete maturation of cultured human leukemia cells
Monocyte maturation markers were induced in cultured human myeloblastic ML-2 leukemia cells after treatment for 1-6 days with 0.03-30 ..mu..M ..delta../sup 9/-tetrahydrocannabinol (THC), the major psychoactive component of marijuana. After a 2-day or longer treatment, 2- to 5-fold increases were found in the percentages of cells exhibiting reactivity with either the murine OKM1 monoclonal antibody of the Leu-M5 monoclonal antibody, staining positively for nonspecific esterase activity, and displaying a promonocyte morphology. The increases in these differentiation markers after treatment with 0.03-1 ..mu..M THC were dose dependent. At this dose range, THC did not cause an inhibition of cell growth. The THC-induced cell maturation was also characterized by specific changes in the patterns of newly synthesized proteins. The THC-induced differentiation did not, however, result in cells with a highly developed mature monocyte phenotype. However, treatment of these incompletely matured cells with either phorbol 12-myristate 13-acetate of 1..cap alpha..,25-dihydroxycholecalciferol, which are inducers of differentiation in myeloid leukemia cells (including ML-2 cells), produced cells with a mature monocyte morphology. The ML-2 cell system described here may be a useful tool for deciphering critical biochemical events that lead to the cannabinoid-induced incomplete cell differentiation of ML-2 cells and other related cell types. Findings obtained from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.
- Research Organization:
- Argonne National Lab., IL (USA)
- DOE Contract Number:
- W-31109-ENG-38
- OSTI ID:
- 5164483
- Journal Information:
- Proc. Natl. Acad. Sci. U.S.A.; (United States), Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States) Vol. 84:15; ISSN PNASA
- Country of Publication:
- United States
- Language:
- English
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
AMINO ACIDS
ANIMAL CELLS
ANIMALS
ANTIBODIES
AUTORADIOGRAPHY
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BIOLOGICAL MARKERS
BIOLOGICAL MATERIALS
BLOOD
BLOOD CELLS
BODY FLUIDS
CARBOXYLIC ACIDS
CARCINOGENESIS
CARCINOGENS
CELL DIFFERENTIATION
CENTRAL NERVOUS SYSTEM AGENTS
DAYS LIVING RADIOISOTOPES
DISEASES
DOSE-RESPONSE RELATIONSHIPS
DRUGS
ELECTROPHORESIS
ESTERS
EVEN-ODD NUCLEI
HALLUCINOGENS
HEMIC DISEASES
HERBS
ISOTOPES
LEUKEMIA
LEUKOCYTES
LIGHT NUCLEI
LIPOTROPIC FACTORS
MAMMALS
MAN
MARIHUANA
MATERIALS
METHIONINE
MONOCLONAL ANTIBODIES
MONOCYTES
NEOPLASMS
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PATHOGENESIS
PHORBOL ESTERS
PLANTS
PRIMATES
PSYCHOTROPIC DRUGS
RADIOISOTOPES
SULFUR 35
SULFUR ISOTOPES
TUMOR CELLS
TWO-DIMENSIONAL ELECTROPHORESIS
VERTEBRATES