Linked Life Data

6586286

Source:http://linkedlifedata.com/resource/pubmed/id/6586286

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1984-7-12
pubmed:abstractText
The effect of various classes of differentiation-inducing agents on macromolecular synthesis was studied in a human myeloblastic leukemia cell line (ML-1). Antineoplastic drugs such as 1-beta-D-arabinofuranosylcytosine, daunorubicin, and actinomycin D caused early inhibition of DNA synthesis, which generally preceded the accrual of differentiation markers. In contrast, retinoic acid and conditioned medium from mitogen-stimulated leukocytes caused a delayed decline in DNA synthesis, which accompanied the appearance of maturing morphology. With 12-O-tetradecanoylphorbol-13-acetate, the decline in DNA synthesis was temporally linked to the onset of maturation, and this agent evidenced some properties of both the antineoplastic agents and the more physiological inducers, retinoic acid and conditioned medium. Antineoplastic agents and conditioned medium, when applied simultaneously, induced differentiation in an additive or synergistic manner, simulating the effects of 12-O-tetradecanoylphorbol-13-acetate. RNA and protein synthesis continued during maturation induced with all these agents, although a partial reduction in RNA synthesis was observed at later time points (greater than or equal to 24 hr). Agents incapable of inducing differentiation, such as cordycepin and cycloheximide, were characterized by a lack of sustained inhibition of DNA synthesis and/or by early (3 hr) inhibition of RNA or protein synthesis. The decline in DNA synthesis caused by the inducing agents was accompanied by decreased cell cycle progression, cells accumulating largely in G1 phase. With daunorubicin and actinomycin D, block of the G1-S transition was evident at 24 hr, whereas with conditioned medium and retinoic acid, accumulation in G1 occurred in a progressive fashion, greater than 77% of cells residing in this phase on Day 6. Maximal inducing doses of 12-O-tetradecanoylphorbol-13-acetate (greater than 80% differentiation) caused an accumulation of cells in G1, as well as an accumulation of cells with a G2-M-phase DNA content (approximately 40%). These observations indicate that early inhibition of DNA synthesis, with sparing of RNA and protein synthesis, is characteristic of the differentiation-inducing antineoplastic drugs examined. These agents may induce differentiation by inhibition of the proliferation path, whereas conditioned medium and retinoic acid may act by the stimulation of differentiation paths. Differentiation can be enhanced by the simultaneous application of agents targeting both of these paths.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
44
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2421-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
1984
pubmed:articleTitle
Macromolecular and cell cycle effects of different classes of agents inducing the maturation of human myeloblastic leukemia (ML-1) cells.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't