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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
1990-6-14
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pubmed:abstractText |
In order to elucidate the mechanism by which the intercalative antineoplastic drug 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA) stabilizes the covalent topoisomerase II-DNA cleavage complex, the effect of the drug on the DNA cleavage/religation reaction of the type II enzyme from Drosophila melanogaster was examined. At a concentration of 60 microM, m-AMSA enhanced topoisomerase II mediated double-stranded DNA breakage approximately 5-fold. Drug-induced stabilization of the enzyme-DNA cleavage complex was readily reversed by the addition of EDTA or salt. When a DNA religation assay was utilized, m-AMSA was found to inhibit the topoisomerase II mediated rejoining of cleaved DNA approximately 3.5-fold. This result is similar to that previously reported for the effects of etoposide on the activity of the Drosophila enzyme [Osheroff, N. (1989) Biochemistry 28, 6157-6160]. Thus, it appears that structurally disparate classes of topoisomerase II targeted antineoplastic drugs stabilize the enzyme's DNA cleavage complex primarily by interfering with the ability of topoisomerase II to religate DNA.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/4'-(9-acridinylamino)methanesulfonan...,
http://linkedlifedata.com/resource/pubmed/chemical/Aminacrine,
http://linkedlifedata.com/resource/pubmed/chemical/Aminoacridines,
http://linkedlifedata.com/resource/pubmed/chemical/Amsacrine,
http://linkedlifedata.com/resource/pubmed/chemical/Antineoplastic Agents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Polymerase II,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type II
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-2960
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
13
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pubmed:volume |
29
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2511-5
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pubmed:dateRevised |
2007-11-14
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pubmed:meshHeading |
pubmed-meshheading:2159323-Aminacrine,
pubmed-meshheading:2159323-Aminoacridines,
pubmed-meshheading:2159323-Amsacrine,
pubmed-meshheading:2159323-Animals,
pubmed-meshheading:2159323-Antineoplastic Agents,
pubmed-meshheading:2159323-Culture Techniques,
pubmed-meshheading:2159323-DNA,
pubmed-meshheading:2159323-DNA Damage,
pubmed-meshheading:2159323-DNA Polymerase II,
pubmed-meshheading:2159323-DNA Topoisomerases, Type II,
pubmed-meshheading:2159323-Drosophila melanogaster,
pubmed-meshheading:2159323-Enzyme Stability
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pubmed:year |
1990
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pubmed:articleTitle |
Stabilization of the topoisomerase II-DNA cleavage complex by antineoplastic drugs: inhibition of enzyme-mediated DNA religation by 4'-(9-acridinylamino)methanesulfon-m-anisidide.
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pubmed:affiliation |
Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0146.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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