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Laser Flow Cytometric Studies on the Intracellular Fluorescence of Anthracyclines¹

Comprehensive Cancer Center for the State of Florida [A. K.] and Department of Oncology [A. K., R. G.], University of Miami School of Medicine, Miami, Florida 33101

We have used a laser flow cytometer to excite and quantitate the intracellular fluorescence of cells exposed in vitro and in vivo to various anthracyclines. In cells exposed to Adriamycin (ADR), intracellular drug fluorescence appeared slowly and reached a peak after 4 hr of incubation. Cells incubated with 10 µg/ml were 5 times more fluorescent than were cells incubated with 1 µg/ml. Cells exposed to daunomycin were 2 to 4 times more fluorescent than were cells similarly exposed to ADR, and the intracellular appearance of daunomycin fluorescence was much more rapid. Cells exposed to N-trifluoroacetyladriamycin and carminomycin had higher amounts of intracellular fluorescence (2 to 4 times), and peak values were reached much more rapidly than in cells exposed to ADR. In cells exposed to rubidazone, fluorescence increased 2- to 4- fold with increased drug concentration and length of exposure. In contrast, nogalamycin fluorescence reached a peak after 60 min of incubation, and a 10-fold increase in drug concentration increased fluorescence only 2-fold.

In animals given injections of ADR (4 mg/kg) and sacrificed after 3 hr, drug fluorescence could be detected in tumor and spleen cells. In contrast, fluorescence in heart nuclei was barely recognizable. However, incubation of isolated nuclei in ADR (1 µg/ml) showed that bone marrow and heart nuclei had greater amounts of ADR fluorescence (2- to 3-fold) than did spleen or liver nuclei similarly treated. The use of laser flow cytometry for monitoring intracellular anthracycline transport, binding, and efflux is demonstrated.

¹ This work was supported by Grants CA-23688 and CA-14395 from the National Cancer Institute, USPHS.

² To whom requests for reprints should be addressed, at Comprehensive Cancer Center (R-71), University of Miami Medical School, P. O. Box 016960, Miami, Fla. 33101.

Received 4/21/80. Accepted 7/21/80.

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