Differentiation of HL-60 promyelocytes to granulocytes induced via the activation of protein kinase-C by benzene
- Rutgers-the State Univ., Piscataway, NJ (United States) Thomas Jefferson Univ., Philadelphia, PA (United States)
Benzene is a hematotoxin which affects the development of bone marrow progenitor cells and a leukemogen which causes acute myelogenous leukemia. The authors studied the effect of benzene on the differentiation of progenitors of the myeloid lineage, using HL-60 promyelocytic leukemia cells which can be induced to differentiate to granulocytes via the activation of protein kinase-C (PKC) by DMSO and retinoic acid. Exposure of HL-60 cells to 5 mM benzene for 5 min. results in the activation of PKC as measured by an increases in the phosphorylation of cellular proteins in a whole cell assay including proteins pp17 and pp27 reported by Feuerstein and Cooper to be involved in HL-60 cell differentiation. The increase in protein phosphorylation observed with benzene was equally as great as that observed with 100 ng/mL PMA, used as a control. Under the same conditions, benzene induces differentiation of the promyelocytes into granulocytes as measured by the acquisition of superoxide production and granulocyte morphology. Preincubation with 40 {mu}M sphinganine, a PKC inhibitor, prevents the benzene-induced increase in cellular protein phosphorylation and the differentiation to granulocytes. These results indicate that benzene, by activation of PKC, can affect myeloid differentiation which may play a role in the ability of benzene to cause acute myelogenous leukemia.
- OSTI ID:
- 5145262
- Report Number(s):
- CONF-9104107--
- Journal Information:
- FASEB Journal (Federation of American Societies for Experimental Biology); (United States), Journal Name: FASEB Journal (Federation of American Societies for Experimental Biology); (United States) Vol. 5:5; ISSN FAJOE; ISSN 0892-6638
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMAL CELLS
AROMATICS
BENZENE
BIOLOGICAL EFFECTS
CELL DIFFERENTIATION
CHEMICAL REACTIONS
DISEASES
ENZYME ACTIVITY
ENZYMES
HYDROCARBONS
IMMUNE SYSTEM DISEASES
LEUKEMIA
NEOPLASMS
ORGANIC COMPOUNDS
PATHOGENESIS
PHOSPHORUS-GROUP TRANSFERASES
PHOSPHORYLATION
PHOSPHOTRANSFERASES
PROTEINS
TRANSFERASES
TUMOR CELLS