Linked Life Data

8747599

Source:http://linkedlifedata.com/resource/pubmed/id/8747599

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7-8
pubmed:dateCreated
1997-2-11
pubmed:abstractText
Previous results from this laboratory indicated that EMT6 cells treated with inhibitors of the intracellular pH (pHi) regulatory mechanisms were resistant to cisplatin (Laurencot, C.M.; Kennedy, K.A. The effect of low pH on the cytotoxicity of cisplatin in EMT6 mouse mammary tumor cells. Oncol. Res. 7:371-380; 1995.) This inhibitor-induced cisplatin resistance was independent of pH. The purpose of the research presented here was to characterize further cisplatin resistance observed in cells cultured with the Na+/H+ antiport inhibitor 5-(N,N hexamethylene) amiloride (NHMA) and the HCO3-/Cl- exchanger inhibitor 4-acetamido-4'-isothiocyanostilbene-2,2'-disulfonic acid (SITS). Using [195mPt]-DDP, the accumulation of cisplatin into EMT6 mouse mammary tumor cells treated with NHMA and SITS was not changed. Total DNA cross-link formation and DNA-interstrand cross-link formation, however, decreased in NHMA- and SITS-treated cells. Since cisplatin accumulation was unchanged in NHMA- and SITS-treated cells but the amount of DNA cross-links decreased, the intracellular activation of cisplatin appeared to be altered in the cisplatin-resistant cells. Because SITS interferes with chloride transport and chloride has been proposed to be involved in cisplatin activation, cisplatin toxicity in EMT6 cells was evaluated in chloride-deficient medium. EMT6 cells cultured in chloride-deficient medium were less sensitive to cisplatin than cells cultured in chloride-containing medium, but this sensitivity was not altered by NHMA and SITS. Furthermore, the resistance to cisplatin in cells treated with NHMA and SITS was similar in chloride-containing and chloride-deficient medium. These data suggest that the concentration of other ions, in addition to chloride, may be important for cisplatin toxicity.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0965-0407
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
363-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Inhibitors of intracellular pH regulation induce cisplatin resistance in EMT6 mouse mammary tumor cells.
pubmed:affiliation
Department of Pharmacology, George Washington University Medical Center, Washington, DC 20037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't