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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
13
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pubmed:dateCreated |
1992-8-4
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pubmed:abstractText |
Centrifugal elutriation was used to obtain synchronized cell populations in various cell cycle phases without prior growth-perturbing manipulation. Treatment of these subpopulations with novobiocin (NOVO), a putative inhibitor of the mammalian topoisomerase II enzyme, revealed a unique cell cycle phase-dependent cytotoxicity for this agent. At a concentration of 0.3 mM, NOVO was cytotoxic only to a specific cell subpopulation in the G1-S phase boundary. Cells in other cell cycle phases were completely unaffected. Additionally, S and G2M phase cells progressed through the cell cycle relatively unaffected by NOVO but were blocked at the G1-S boundary. NOVO treatment protected tumor cells from Adriamycin (ADR)-induced lethality but sensitized them to the toxic action of 4-hydroperoxycyclophosphamide, and alkylating agent. These opposing effects of NOVO were demonstrated in all of the four tumor cell lines investigated: A431 and HEp3 (derived from human squamous cell carcinomas); MLS, a human ovarian cancer cell line; and a Chinese hamster ovary cell line. The degree of protection against ADR was the greatest for S-phase cells, intermediate for cells in early G1 and M phases, and the least for late G1 cells. This cell cycle-dependent protection by NOVO, which is identical to the cell cycle-dependent cytotoxicity of ADR, was consistent with the idea that NOVO interfered directly with the cell-killing mechanism of ADR. In contrast, even though the cytotoxic activity of 4-hydroperoxycyclophosphamide exhibited significant cell cycle dependency, NOVO enhanced 4-hydroperoxycyclophosphamide lethality equally for all cell cycle phases.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclophosphamide,
http://linkedlifedata.com/resource/pubmed/chemical/Doxorubicin,
http://linkedlifedata.com/resource/pubmed/chemical/Glutathione,
http://linkedlifedata.com/resource/pubmed/chemical/Novobiocin,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/perfosfamide
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
0008-5472
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
52
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
3515-20
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:1319822-Animals,
pubmed-meshheading:1319822-Cell Cycle,
pubmed-meshheading:1319822-Cell Line,
pubmed-meshheading:1319822-Cell Survival,
pubmed-meshheading:1319822-Cyclophosphamide,
pubmed-meshheading:1319822-Doxorubicin,
pubmed-meshheading:1319822-Glutathione,
pubmed-meshheading:1319822-Novobiocin,
pubmed-meshheading:1319822-Topoisomerase I Inhibitors
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pubmed:year |
1992
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pubmed:articleTitle |
Modulation of the cell cycle-dependent cytotoxicity of adriamycin and 4-hydroperoxycyclophosphamide by novobiocin, an inhibitor of mammalian topoisomerase II.
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pubmed:affiliation |
Tumor Biology Division, University of Rochester Cancer Center, New York 14642.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.
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