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Title: 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 obtainedmore » from this system may have important implications for studies of cannabinoid effects on normal human bone-marrow progenitor cells.« less
Authors:
; ; ; ;
Publication Date:
OSTI Identifier:
5164483
DOE Contract Number:
W-31-109-ENG-38
Resource Type:
Journal Article
Resource Relation:
Journal Name: Proc. Natl. Acad. Sci. U.S.A.; (United States); Journal Volume: 84:15
Research Org:
Argonne National Lab., IL (USA)
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.; MARIHUANA; BIOLOGICAL EFFECTS; TUMOR CELLS; AUTORADIOGRAPHY; CELL DIFFERENTIATION; BIOLOGICAL MARKERS; CARCINOGENESIS; DOSE-RESPONSE RELATIONSHIPS; HALLUCINOGENS; LEUKEMIA; MAN; METHIONINE; MONOCLONAL ANTIBODIES; MONOCYTES; PHORBOL ESTERS; SULFUR 35; TWO-DIMENSIONAL ELECTROPHORESIS; AMINO ACIDS; ANIMAL CELLS; ANIMALS; ANTIBODIES; BETA DECAY RADIOISOTOPES; BETA-MINUS DECAY RADIOISOTOPES; BIOLOGICAL MATERIALS; BLOOD; BLOOD CELLS; BODY FLUIDS; CARBOXYLIC ACIDS; CARCINOGENS; CENTRAL NERVOUS SYSTEM AGENTS; DAYS LIVING RADIOISOTOPES; DISEASES; DRUGS; ELECTROPHORESIS; ESTERS; EVEN-ODD NUCLEI; HEMIC DISEASES; HERBS; ISOTOPES; LEUKOCYTES; LIGHT NUCLEI; LIPOTROPIC FACTORS; MAMMALS; MATERIALS; NEOPLASMS; NUCLEI; ORGANIC ACIDS; ORGANIC COMPOUNDS; ORGANIC SULFUR COMPOUNDS; PATHOGENESIS; PLANTS; PRIMATES; PSYCHOTROPIC DRUGS; RADIOISOTOPES; SULFUR ISOTOPES; VERTEBRATES 560300* -- Chemicals Metabolism & Toxicology