Effect of 12-O-tetradecanoylphorbol-13-acetate on selection of drug-resistant phenotypes in rodent cells.

The effect of the tumour promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on the selection of drug-resistant phenotypes in hamster and mouse cells has been studied. TPA increased considerably the incidence of methotrexate (MTX)-, N-(phosphonacetyl)-L-aspartate- and cadmium-resistant 3T6 and 3T3 mouse cell clones, but it had little effect on V79 and CHO hamster cells. The MTX-resistant V79 hamster cell clones, selected with or without TPA, lost their resistance within 15 cell cycles, however, 50% of the 3T6 mouse cell clones selected and maintained in the presence of TPA preserved their resistance for more than 15 cell cycles. A number of the MTX-resistant 3T6 clones overproduced dihydrofolate reductase enzyme; however, their frequency was lower among the clones selected in the presence of TPA.