| Resistance of V79 multicell spheroids to mitoxantrone: drug uptake and cytotoxicity. | |
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MedLine Citation:
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PMID: 3454247 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously shown that V79 multicell spheroids are resistant to the anthracenedione mitoxantrone (1). In this paper we demonstrate that this resistance is not solely due to restricted drug penetration into the spheroid, but also to an altered intrinsic resistance of the cells when grown as a three-dimensional structure. We have studied the uptake and toxicity of mitoxantrone in V79-OCF4 monolayers, 100 micron spheroids, 650 micron spheroids, and outer and inner cells of 650 micron spheroids. The LD90 for cells exposed as monolayers to mitoxantrone for two hours was 0.016 microgram/ml, 0.055 microgram/ml for 100 micron spheroids, 1.5 micrograms/ml for outer spheroid cells and 6.2 micrograms/ml for inner spheroid cells. Uptake of [14C]mitoxantrone was linear for all populations with no plateau up to the highest doses used. The uptake of drug required to kill 90% of the cells in a population (UP90) of monolayers was 3.7 ng/10(6) cells, 10.7 ng/10(6) cells for 100 micron spheroids, 169 ng/10(6) cells for outer spheroid cells, and 146 ng/10(6) cells for inner spheroid cells. The relative resistance of spheroids compared to monolayers, based on drug concentration in the medium, was 3.4 for small spheroids, 92 for outer cells, and 390 for inner cells. When cell survival was normalized to drug uptake, the relative resistance of spheroids to monolayers was 2.9 for small spheroids, 46 for outer cells and 40 for inner cells of large spheroids. The data demonstrate that the resistance of multicell spheroids to mitoxantrone is not solely due to restricted drug penetration into the cell aggregate but is also due to a spheroid-induced altered intrinsic resistance of the V79 cells. |
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Authors:
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T J Bichay; W R Inch |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Cancer drug delivery Volume: 4 ISSN: 0732-9482 ISO Abbreviation: Cancer Drug Deliv Publication Date: 1987 |
Date Detail:
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Created Date: 1988-09-16 Completed Date: 1988-09-16 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8409965 Medline TA: Cancer Drug Deliv Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 201-11 Citation Subset: IM |
Affiliation:
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Department of Medical Biophysics, University of Western Ontario, London, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cell Survival
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drug effects Cells, Cultured Drug Resistance Mitoxantrone / pharmacokinetics, pharmacology* |
| Chemical | |
Reg. No./Substance:
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65271-80-9/Mitoxantrone |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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