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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
1998-4-15
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pubmed:abstractText |
Clones of human colon carcinoma (WiDr), ovarian carcinoma (SK-OV-3), and Chinese hamster V79 cells expressing the nitroreductase enzyme (NR) from E. coli B were 52-, 225- and 177-fold respectively more sensitive to a 24-h incubation with the prodrug 5-(aziridin-1-yl)-2,4-dinitrobenzamide (CB1954) than the parent lines. The IC50s of non-NR-expressing bystander cells were measured in the presence of differing proportions of NR-expressing cells. The shift in IC50 was used to calculate a value for the bystander effect, termed the transmission efficiency (TE), which is the decrease in IC50 due to bystander effect as a percentage of the maximum decrease possible. The percentage of NR-expressing cells for which the TE was 50%, (the TE50) is a single datum of bystander efficacy. WiDr and V79 cell lines, had a similar TE50 of approximately 2%. SK-OV-3 gave a lower value of 0.3%. These TE50 correlate with concentrations of cytosolic NR activity, which is distinguished from endogenous DT diaphorase activity by kinetic differences. A novel method is described which enables both DNA crosslinks and drug-induced single-strand breaks to be simultaneously quantified in a sedimentation assay. Using this technique, bystander DNA damage was demonstrated in V79 cells, of approximately 50% of that in activator cells.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0969-7128
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
5
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
105-12
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9536271-Aziridines,
pubmed-meshheading:9536271-DNA Damage,
pubmed-meshheading:9536271-Escherichia coli,
pubmed-meshheading:9536271-Gene Expression,
pubmed-meshheading:9536271-Gene Therapy,
pubmed-meshheading:9536271-Humans,
pubmed-meshheading:9536271-Neoplasms,
pubmed-meshheading:9536271-Nitroreductases,
pubmed-meshheading:9536271-Prodrugs,
pubmed-meshheading:9536271-Transfection,
pubmed-meshheading:9536271-Tumor Cells, Cultured
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pubmed:year |
1998
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pubmed:articleTitle |
Gene-directed enzyme prodrug therapy: quantitative bystander cytotoxicity and DNA damage induced by CB1954 in cells expressing bacterial nitroreductase.
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pubmed:affiliation |
Cancer Research Campaign Centre for Cancer Therapeutics, Institute of Cancer Research, Sutton, UK.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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