ISOLATION AND PRELIMINARY CHARACTERIZATION OF AN ADRIAMYCIN-RESISTANT MURINE FIBRO-SARCOMA CELL-LINE

Abstract

A variant cell line (UV-2237-ADMR) resistant to the anthracycline antibiotic Adriamycin (doxorubicin) was selected in vitro from the murine UV-2237 fibrosarcoma tumor cell line. Resistance to Adriamycin proved to be a stable characteristic of the UV-2237-ADMR line, whether the line was grown in vivo or in vitro. The UV-2237-ADMR line also exhibited increased resistance to N-trifluoroacetyladriamycin-14-valerate, daunorubicin, actinomycin D, amsacrine, mitomycin C, vinblastine and vincristine but not to bleomycin. Cell-cell hybridization studies showed that the Adriamycin resistance is an incompletely dominant trait. Uptake and efflux studies with [14C]Adriamycin indicated that the resistance exhibited by the UV-2237-ADMR line was due to both reduced uptake of the drug and an increased active efflux.