Linked Life Data

15126352

Source:http://linkedlifedata.com/resource/pubmed/id/15126352

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2004-5-5
pubmed:abstractText
Tamoxifen (TAM) possesses antiestrogen activity and is widely used for the treatment or prevention of breast cancer. However, it is also carcinogenic in human uterus and rat liver, highlighting the profound complexity of its actions. To explore the molecular mechanisms of TAM-induced mutagenesis, we analyzed the effects of this drug on gene-disrupted chicken B lymphocyte (DT40) clones deficient in various DNA repair pathways. Rad18, Rev3, and Polkappa are involved in translesion DNA synthesis (TLS), which facilitates recovery from replication blocks on damaged template strands. DT40 cells deficient in TLS were found to be hypersensitive to TAM, exhibiting an increase in chromosomal breaks. Furthermore, these mutants were also hypersensitive to 4-hydroxyestradiol, a physiological metabolite of estrogen. These data suggest a contribution of TLS to the prevention of chromosomal breaks by TAM and estrogen, and they therefore indicate that such error-prone DNA synthesis underlies mutagenesis induced by these agents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
64
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3144-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Extensive chromosomal breaks are induced by tamoxifen and estrogen in DNA repair-deficient cells.
pubmed:affiliation
Department of Radiation Genetics, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't