Linked Life Data

8380128

Source:http://linkedlifedata.com/resource/pubmed/id/8380128

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1993-1-25
pubmed:abstractText
We have developed a simple system for determining the specific contribution of topoisomerase II targeting to the cytotoxic activity of a drug. We have constructed yeast strains that are permeable to anti-topoisomerase II drugs, carry a DNA repair mutation, rad52, and also have a temperature sensitive topoisomerase II mutation, top2-1. Strains carrying the top2-1 mutation have nearly normal topoisomerase II activity at 25 degrees C but less than 10% of wild type activity at 36 degrees C. We find that at a semi-permissive temperature (30 degrees C), there is sufficient topoisomerase II activity for viability; but since the topoisomerase II activity is greatly reduced, the cells are very resistant to anti-topoisomerase II drugs. Conversely, such cells are hypersensitive to the topoisomerase I inhibitor camptothecin. These results provide strong support for the model that drug stabilized DNA cleavage, rather than a lack of enzyme activity, is responsible for cell killing by eukaryotic anti-topoisomerase II agents. They also show that there is a minimum level of topoisomerase II activity in yeast that is consistent with viability but also allows a high degree of resistance to anti-topoisomerase II agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:geneSymbol
top2-1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
89-93
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
A temperature sensitive topoisomerase II allele confers temperature dependent drug resistance on amsacrine and etoposide: a genetic system for determining the targets of topoisomerase II inhibitors.
pubmed:affiliation
Division of Hematology/Oncology, Children's Hospital of Los Angeles, California 90027.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't