Linked Life Data

8242628

Source:http://linkedlifedata.com/resource/pubmed/id/8242628

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1994-1-3
pubmed:abstractText
Hypoxic cells in tissue pose many medical problems, and there is a need for more accurate measurements of tissue hypoxia. However, measurement of the pO2 and the extent of hypoxia within normal and tumor tissue have proven difficult. One of the most sensitive of the currently available methodologies involves the oxygen-dependent metabolic activation of nitroheterocyclic drugs, leading to adducts between the drugs and cellular macromolecules. Limitations of the present drugs and adduct-detection methods prompted the present studies. A pentafluorinated derivative [EF5; 2-(2-nitro-1H-imidazol-1-yl)-N-(2,2,3,3,3-pentafluoropropyl)acetam ide] of etanidazole was synthesized with the expectation of lessening some of the non-oxygen-dependent variability in adduct formation observed previously with other nitroaromatic compounds. EF5-protein conjugates, prepared by radiochemical reduction, were found to be immunogenic and allowed the development of monoclonal antibodies. One of these antibodies, ELK2-4, has been characterized and found to be highly specific for the EF5 adducts whether produced radiochemically or by cellular bioreductive metabolism. 9L rat glioma cells pretreated with EF5 under hypoxic, compared with aerobic, conditions were readily discriminated immunochemically using fluorochrome-conjugated secondary antibodies which recognize the ELK2-4 antibody subtype (IgG1). Similarly, the central region of multicenter spheroids, composed of EMT6 mouse mammary sarcoma cells, was selectively visualized by immunohistochemistry after the spheroids were incubated for 4 h in 0.5 mM EF5. Tumor biopsy, preparation, and immunohistochemical staining 24 h after treatment of tumor-bearing animals with drug also demonstrated high contrast regions within EMT6 mouse or Morris 7777 hepatoma rat tumors. The use of this new compound and its highly specific monoclonal antibody may allow elucidation of bioreductive metabolism of the nitroheterocyclics and significantly improve technologies for the quantitation of tissue pO2.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
53
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5721-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1993
pubmed:articleTitle
Detection of hypoxic cells by monoclonal antibody recognizing 2-nitroimidazole adducts.
pubmed:affiliation
Cancer Center, University of Rochester, New York 14642.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't