Drug resistance in Chinese hamster lung and mouse tumor cells.

Studies of Chinese hamster and mouse cells with high levels of acquired resistance to dactinomycin, daunorubicin, or vincristine have shown that these different permeability mutants all display similar phenotypic alterations: dramatic changes toward normal cell morphology and growth behavior and substantially reduced oncogenic potential. All three resistant cell types show increased expression of a high molecular weight plasma membrane glycoprotein species, gp150. Uniquely, vincristine-resistant cells contain gene amplification-associated chromosome abnormalities (homogeneously staining regions or double minute chromosomes), and they oversynthesize a low molecular weight cytosolic protein (V19). Cells grown in the absence of drug are phenotypically unstable. Revertant cells decline in resistance, length or number of homogeneously staining regions or double minute chromosomes, and expression of gp150 and V19. These proteins are thus candidate products of amplified genes which may or may not be manifested cytogenetically. The phenomena of drug resistance and reverse transformation are currently being addressed in protein phosphorylation studies.