DRUG-RESISTANCE OF DOXORUBICIN-RESISTANT CHO CELL-LINE

Some characteristics of doxorubicin-resistant CHO cell line (RC1) were studied by means of cell biological methods and SDS-PAGE electrophore sis. The resistance factor was 16.5-fold, and RC1 revealed cross-resis tances to colchicine, actinomycin and harringtonine. By indirect immun ofluorescence assay, P-glycoprotein was not detected. Compared with CP O, the doxorubicin (Dox) uptake and accumulation of RC1 decreased, but the membrane fruidity of RC1. increased. The reduction in drug accumu lation was correlated with increase in membrane fluidity. Dox was main ly distributed in the cell nucleus of CHO, but in both cytoprasm and n ucleus of RC1. This suggested that Dox was transported more slowly in RC1 cytoplasm than in CHO cytoplasm, resulting in less Dox entrance in to the cell nucleus of RC1 than into that of CHO. We also found that a 30-40 kDa nuclear protein which was expressed normally in CHO disappe ared in RC1.