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.
D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations; D003609:Dactinomycin / Q000494:pharmacology*; D004351:Drug Resistance; D005784:Gene Amplification; D051379:Mice; D008970:Molecular Weight; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D009374:Neoplasms, Experimental / Q000235:genetics*; D014750:Vincristine / Q000494:pharmacology*
D009363:Neoplasm Proteins; D003609:Dactinomycin; D014750:Vincristine