A close association of adriamycin resistance with expression of cell surface antigens in adriamycin-resistant cell lines of herpes simplex virus type 2-transformed Syrian hamster cells.

Abstract

We determined the properties of three adriamycin (ADM)-resistant cell lines isolated from a clone of herpes simplex virus (HSV) type 2-transformed Syrian hamster cells. The ADM-resistant lines (ADMR-6, -7 and -9) established by continuous exposure of the cells to ADM were 20 to 30 times more resistant to ADM than was the parent line. These resistant lines exhibited cross-resistance to daunomycin, actinomycin D, chromomycin A3 and vincristine, but not to mitomycin C, bleomycin or methotrexate. Uptake and efflux studies with [3H]ADM indicated that one line (ADMR-9) incorporated and retained lesser amounts of [3H]ADM than did the parent line but the other two lines accumulated and retained as much of the drug as did the parent line. Expression of cell surface antigens, detected by immunofluorescence tests with antiserum to HSV type 1, was at a low level (about 8% positive) in the parent line after replating of the cells, although it was enhanced by treatment of the cells with ADM (0.25 micrograms/ml). However, the antigens were strongly expressed (greater than or equal to 35% positive) on the surface of cells of the three resistant lines in the absence of ADM. Both antigen expression and ADM resistance of the cells were relatively stable in in vitro cultivation but were unstable in in vivo cultivation, suggesting that the constitutive expression of the antigens is closely associated with the phenotype of ADM resistance.