Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2000-8-24
pubmed:abstractText
DNA topoisomerase II is an essential nuclear enzyme that modulates DNA topology during multiple cellular processes such as DNA replication and chromosome segregation. Several important clinical antitumor drugs and antibiotics act through inhibition of topoisomerase II. There are a number of different steps in the action of topoisomerase II, all of which are potential targets for inhibition through drugs and also for cellular and genetic toxicity as well as for mutagenesis. We have investigated and compared the genotoxicity and mutagenicity of the mechanistically different topoisomerase II inhibitors m-amsacrine, mitoxantrone, etoposide, genistein, ICRF 193, and berenil using the in vitro micronucleus test, single cell gelelectrophoresis (comet assay) and the mutation assay (tk-locus) in L5178Y mouse lymphoma cells. All six compounds induced micronuclei and all except berenil were mutagenic. M-amsacrine, mitoxantrone, etopside and genistein induced DNA migration in the comet assay, whereas ICRF 193 was only weakly positive and berenil was negative in this test. Our results are in good agreement with the compounds' proposed mechanisms of interaction with topoisomerase II.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0378-4274
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
116
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7-16
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Genotoxicity of several clinically used topoisomerase II inhibitors.
pubmed:affiliation
Department of Toxicology, University of Würzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't