The use of genetic marking to assess the interaction of sensitive and multidrug-resistant cells in mixed culture.

The interaction of normal (CHO-K1) and multidrug-resistant (Adrr) Chinese hamster ovary cells was examined in mixed monolayer and spheroid culture. In order to assess the individual response of the two cell types in mixed culture, CHO-K1 was genetically marked by transfection with a bacterial beta-galactosidase gene. The enzyme product can be detected histochemically and allows identification of the marked cell line, designated CHO-K1-BG. Following administration of doxorubicin or mitozantrone, there was a large difference in the clonogenic survival of CHO-K1-BG and Adrr, whereas the overall survival of a 50:50 mixture of the two cell lines had intermediate values. When the survival of marked and unmarked colonies from mixed culture was assessed separately, there was no detectable alteration in chemosensitivity. We have found no evidence for interaction of sensitive and multidrug-resistant cells in this system.