Linked Life Data

3731072

Source:http://linkedlifedata.com/resource/pubmed/id/3731072

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
1986-9-17
pubmed:abstractText
The potential mechanisms of the extremely potent anthracycline analogue 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin (MRA-CN) have been compared with those of doxorubicin (DOX) by examination of drug effects on colony formation, macromolecular synthesis, DNA integrity, and ultrastructure of human leukemia cells in vitro. Following a 1-h exposure, MRA-CN was found to be 1400-fold more cytocidal than DOX which correlated with the drugs' inhibitory effects on DNA and total RNA synthesis. Treatment with MRA-CN resulted in a dose-dependent production of DNA interstrand cross-links as quantified by alkaline elution. One-h treatments with DOX or 3'-deamino-3'-(4-morpholinyl) doxorubicin (the non-cyano-containing analogue of MRA-CN) produced no DNA-DNA cross-links; rather they produced protein-concealed DNA single-strand breaks. After removal of MRA-CN, the DNA of KBM-3 cells displayed time-dependent fragmentation as indicated by rapid DNA filter elution during the pH 10 lysis step which preceded pH 12 elution. Within 4 h of MRA-CN exposure (10 nM, 1 h), 50% of the cellular DNA was in the lysis fraction. By 24 h, all the cellular DNA was in this fraction. MRA-CN (10 nM), 3'-deamino-3'-(4-morpholinyl)doxorubicin (1 microM), and actinomycin D (1 microM), but not DOX (3 mircroM), each produced distinctive nucleolar macrosegregation, indicating an effect on rRNA synthesis. The alpha-CN substituent on the morpholinyl moiety of MRA-CN appears to be responsible for the unique antitumor potency of this anthracycline. Nucleolar macrosegregation is probably associated with the morpholinyl moiety and is independent of the alpha-CN substituent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:volume
46
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4041-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1986
pubmed:articleTitle
Effects of 3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin and doxorubicin on the survival, DNA integrity, and nucleolar morphology of human leukemia cells in vitro.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.