Resistance to actinomycin D and to vincristine induced in a SEWA mouse tumor cell line with concomitant appearance of double minutes and a low molecular weight protein.

By increasing stepwise the drug concentration of the medium, we have induced, in a cell line of the murine SEWA tumor, resistance to actinomycin D (AMD) and vincristine (VCR) 30-50 times above the normal. In both types of resistant cells, we have revealed, by two-dimensional gel electrophoresis, a protein (MW 21K , pI 5) not found in control cells. Large fractions of the resistant cells contained double minutes (DM). In AMD-resistant cells, correlation was demonstrated between number of DM and degree of resistance. Back in AMD-free medium, resistant cells lost both the DM and the 21K protein. Cross-resistance prevailed between AMD and VCR. Cells resistant to AMD and VCR showed erratic resistance to methotrexate (MTX), but no significant resistance existed in the reverse direction.