Abstract
A marked gradient of Adriamycin uptake in cells of tissue-like multicell spheroids in vitro has been demonstrated by fluorescence photomicroscopy and flow microfluorimetry techniques. As expected, this gradient led to an increased net survival for cells from Adriamycin-treated spheroids relative to monolayers and markedly greater clonogenicity of central spheroid cells than external cells selected by fluorescence-activated cell sorting. Growth of cells as spheroids seemed to impart an additional degree of drug resistance relative to cells grown as monolayers, in that equal toxicity required greater intracellular fluorescence (and thus more Adriamycin) for the spheroid cells. The flow cytometry techniques thus provide a mechanism for quantification of Adriamycin penetration into spheroids and provide a method for selection of cells from various depths within the spheroid.
Footnotes
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↵1 This research was supported by Grant CA 23511 awarded by the National Cancer Institute, Department of Health, Education, and Welfare.
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↵2 To whom requests for reprints should be addressed.
- Received January 12, 1981.
- Accepted June 16, 1981.
- ©1981 American Association for Cancer Research.