Effect of aphidicolin on Friend erythroleukemia cell maturation

Journal Article · Sat Feb 28 23:00:00 EST 1987 · Exp. Cell Res.; (United States)

DOI:https://doi.org/10.1016/0014-4827(87)90240-0· OSTI ID:6526745

Beckman, B S; Kopfler, W; Koury, P; Jeter, Jr, J R

Aphidicolin, a specific and reversible inhibitor of DNA polymerase alpha, was examined as a potential tool to evaluate the relationship between proliferative and differentiative events in Friend erythroleukemia cell (FELC) maturation. Since FELC can be induced to differentiate alone the erythrocytic pathway with a variety of inducing agents, the effects of aphidicolin were tested on proliferating FELC and cells which were induced to differentiate with the potent inducer, hexamethylene bisacetamide (HMBA). Exposure of FELC to aphidicolin resulted in unbalanced growth within 24 h, as reflected by abnormally large cells, compared with untreated cells. Continuous exposure of FELC from 24-96 h with doses of aphidicolin ranging from 0.5 to 50 ..mu..M was more effective for differentiation induction than was short-term exposure (1, 2, 4, 12 h) to the drug. When cells were treated with HMBA (5 mM0 and aphidicolin (1, 5, 10 ..mu..M), in combination, aphidicolin shifted the time of onset of differentiation from 72 to 48 h, but did not act synergistically or additively with HMBA. In contrast, suboptimal doses of aphidicolin (0.5 ..mu..M) in combination with HMBA (2.5 mM) produced an additive effect on FELC differentiation. In addition, (/sup 3/H)thymidine experiments demonstrated that aphidicolin reversibly blocked FELC in S phase and at G1-S interface of the cell cycle. These results indicate that aphidicolin can induce the differentiation of FELC, and that a complete round of replicative DNA synthesis is not required for differentiation to occur.

• Research Organization: Tulane Univ. School of Medicine, New Orleans, LA
• OSTI ID: 6526745
• Journal Information: Exp. Cell Res.; (United States), Journal Name: Exp. Cell Res.; (United States) Vol. 169:1; ISSN ECREA
• Country of Publication: United States
• Language: English

Related Subjects

550301* -- Cytology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMAL CELLS
AUTORADIOGRAPHY
AZINES
BIOLOGICAL EFFECTS
CELL CYCLE
CELL DIFFERENTIATION
CELL PROLIFERATION
DISEASES
DNA POLYMERASES
ENZYME INHIBITORS
ENZYMES
HEMIC DISEASES
HETEROCYCLIC COMPOUNDS
LABELLED COMPOUNDS
LEUKEMIA
NEOPLASMS
NUCLEOSIDES
NUCLEOTIDES
NUCLEOTIDYLTRANSFERASES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PHOSPHORUS-GROUP TRANSFERASES
POLYMERASES
PYRIMIDINES
RIBOSIDES
THYMIDINE
TRANSFERASES
TRITIUM COMPOUNDS
TUMOR CELLS