Linked Life Data

2830964

Source:http://linkedlifedata.com/resource/pubmed/id/2830964

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
1988-4-14
pubmed:abstractText
10-[3-Diethylaminopropylamino]-6-methyl-5H-pyrido[3',4':4,5] pyrrolo[2,3-g]isoquinoline (PZE) is an ellipticine derivative currently in clinical trials. PZE has been postulated to produce cellular DNA lesions by an uncommon mechanism. PZE-induced DNA damage was further investigated in L1210 cells in culture. PZE was highly cytotoxic for these cells (90% inhibitory concentration = 3.1 microM). The effects of PZE on cellular DNA were studied first by alkaline sucrose sedimentation, in comparison with those of 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). Like m-AMSA, PZE induced DNA strand breaks which were detected without a proteolytic treatment of the cell lysate. This result rules out the existence of covalent protein bridges sealing DNA termini at the break sites. PZE was less active than m-AMSA. DNA fragmentation was maximum at 5 microM and was lower at higher concentrations. The DNA effects of PZE were also studied by alkaline elution, and compared with those of Adriamycin and m-AMSA. Like Adriamycin, PZE induced single-strand breaks (SSBs) in a bell-shaped manner with respect to drug concentration. The maximum SSB frequency [1784 +/- 370 (SEM) rad equivalents)] was obtained at 16 microM. The kinetics of SSB reversion after drug removal was slower than in the case of m-AMSA. Similar bell-shaped curves were obtained for PZE-induced double-strand breaks and DNA-protein cross-links. PZE induced more double-strand breaks per SSB than did m-AMSA. However, as in the case of m-AMSA, PZE induced equal SSB and DNA-protein cross-link frequencies. These results suggest that PZE induces DNA breaks by inhibiting topoisomerase II as do other antitumor intercalators.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1404-9
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1988
pubmed:articleTitle
Production of protein-associated DNA breaks by 10-[diethylaminopropylamino]-6-methyl-5H-pyrido[3',4':4,5]pyrrolo [2,3-g]isoquinoline in cultured L1210 cells and in isolated nuclei: comparison with other topoisomerase II inhibitors.
pubmed:affiliation
Sanofi Recherche, Toulouse, France.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't