Linked Life Data

2804972

Source:http://linkedlifedata.com/resource/pubmed/id/2804972

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
1989-12-11
pubmed:abstractText
We have reported previously the isolation and characterization of a Chinese hamster ovary cell line, designated CHO-Chlr, which exhibits resistance to bifunctional nitrogen mustards while maintaining sensitivity to a range of other alkylating agents and chemotherapeutic drugs. This enhanced drug resistance is associated with a greater than 40-fold increase in the level of expression of an alpha class (YcYc) glutathione S-transferase (GST) as compared to the parental, CHO-K1, cell line. Here, we have purified GST from CHO-Chlr cells and show that the nonsteroidal antiinflammatory drug indomethacin acts as an inhibitor of enzyme activity. Indomethacin at 500 microM causes no significant decrease in colony forming ability of either CHO-K1 or CHO-Chlr cells. However, the cytotoxicity of chlorambucil is potentiated 5.5-fold in CHO-Chlr cells, but only 2.5-fold in CHO-K1 cells following preexposure to 500 microM indomethacin. In contrast, the antiinflammatory agent acetylsalicylic acid failed to inhibit the activity of purified GST and caused no potentiation of chlorambucil toxicity, suggesting that the potentiation by indomethacin is not due to the effects of this drug on prostaglandin synthesis. These studies provide further evidence that GSTs may be involved in the development of resistance to bifunctional alkylating agents and suggest that indomethacin, or agents with similar activities, may be of value as an adjunct to chemotherapy in some patients with tumors resistant to treatment with alkylating agents.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6265-8
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Possible role of inhibition of glutathione S-transferase in the partial reversal of chlorambucil resistance by indomethacin in a Chinese hamster ovary cell line.
pubmed:affiliation
Leukaemia Research Fund Laboratory, Medical School, University of Newcastle upon Tyne, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't