Resistance and Cross-Resistance of Cultured Leukemia P388 Cells to Vincristine, Adriamycin, Adriamycin Analogs, and Actinomycin D2

Abstract

Cultured P388 cells derived from leukemia P388 passaged in vivo in (C57BL × DBA/2)F₁ mice were approximately one-tenth Iess sensitive to N-trifluoroacetyladriamycin-14-valerate (AD32) and cinerubin A, inasmuch as the concentrations of these agents had to be increased tenfold to produce a reduction in cell viability of the same order of magnitude as that produced by adriamycin, daunomycin, or actinomycin D. Cultured P388 cells derived from resistant cells populations developed in vivo retained their resistance to vincristine. These resistant cells exhibited cross-resistance to actinomycin D, adriamycin, daunomycin, and AD32, but cross-resistance to cinerubin A could not be detected. Data also showed that the vincristine-resistant cells were more sensitive to AD32 (2.8×10^-6) than to adrlamycln (3.4×10^-6M) during a 6-hour exposure of cells to agents.