Linked Life Data

1360213

Source:http://linkedlifedata.com/resource/pubmed/id/1360213

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
1992-12-30
pubmed:abstractText
A series of cell lines derived from Chinese hamster V79 cells by selection in increasing concentrations of Adriamycin (ADRM) was developed to study the mechanisms of drug resistance and its relationship to radiation response. Survival studies revealed that selection in increasingly higher concentrations of ADRM positively correlated with increased cellular drug resistance. Increased cellular resistance correlated positively with amplification of the hamster multidrug-resistance gene (pgp 1) as detected with dot blot analysis using the pCHP1 probe. Southern blot analysis of restriction endonuclease digested DNA (Eco RI, Hind III, Pst I, or Bam HI) showed that (1) some fragments were preferentially amplified compared to others in the ADRM-resistant lines; and (2) no major gene rearrangement appeared to have occurred during the selection for greater ADRM resistance. Levels of pgp 1 gene expression assayed with dot blot and Northern analysis showed a parallel increase of mRNA with gene amplification and increased ADRM resistance. The amounts of the pgp 1 gene product, P-glycoprotein (P-gp), in the cell membrane of the ADRM-resistant cells correlated with the amount of gene amplification/expression. However, levels of P-gp only correlated with degree of drug resistance as measured by cell survival in earlier selection stages (77A and LZ-3). In later selection stages (LZ-8 and LZ-24), higher levels of ADRM resistance were achieved but levels of P-gp did not increase beyond approximately 20% of plasma membrane proteins. These results suggest that (1) the LZ cell plasma membrane may have a physical limit as to the amount of P-gp it can accommodate and/or there is a cellular mechanism for regulating the amount of P-gp in the plasma membrane, and (2) additional resistance mechanisms are present in LZ-8 and LZ-24 cells. Microscopic observations of intracellular drug distribution in these cell lines revealed that (1) ADRM appeared to be sequestered in cytoplasmic vesicles, and (2) the amount of sequestration (number of vesicles) exhibited correlated with the degree of drug resistance attained by the cell lines. These results suggest that drug sequestration is another mechanism of resistance in LZ cells in addition to P-gp-mediated drug efflux.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0006-2952
pubmed:author
pubmed:issnType
Print
pubmed:day
3
pubmed:volume
44
pubmed:geneSymbol
mdr1, pgp 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1859-68
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:1360213-Animals, pubmed-meshheading:1360213-Blotting, Northern, pubmed-meshheading:1360213-Blotting, Southern, pubmed-meshheading:1360213-Cell Line, pubmed-meshheading:1360213-Cell Survival, pubmed-meshheading:1360213-Cricetinae, pubmed-meshheading:1360213-Cricetulus, pubmed-meshheading:1360213-DNA, pubmed-meshheading:1360213-Doxorubicin, pubmed-meshheading:1360213-Drug Resistance, pubmed-meshheading:1360213-Gene Amplification, pubmed-meshheading:1360213-Gene Expression, pubmed-meshheading:1360213-Immunoblotting, pubmed-meshheading:1360213-Intracellular Fluid, pubmed-meshheading:1360213-Membrane Glycoproteins, pubmed-meshheading:1360213-P-Glycoprotein, pubmed-meshheading:1360213-RNA, Messenger, pubmed-meshheading:1360213-Radiation Tolerance, pubmed-meshheading:1360213-Tissue Distribution
pubmed:year
1992
pubmed:articleTitle
Characterization of adriamycin-resistant and radiation-sensitive Chinese hamster cell lines.
pubmed:affiliation
University of Texas Medical Branch, Department of Radiation Therapy, Galveston 77555.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.