TPA enhancement of the recovery of methotrexate and N-phosphonacetyl L-aspartate resistant mouse 3T6 cell clones is associated with transient alterations of cell cycle progression.

The effects of methotrexate (MTX) and N-phosphonacetyl L-aspartate (PALA) with and without 12-O-tetradecanoylphorbol-13-acetate (TPA) have been tested on the cell-cycle traverse of mouse 3T6 and Chinese hamster V79 cell lines. MTX, whether administered with or without TPA, had very little effect on the cell cycle of the V79 Chinese hamster cell line. However, low MTX concentrations produced a significant G1 accumulation in the mouse 3T6 cell line after 24 hr, and this was accentuated by TPA treatment. These findings parallel previous observations that TPA enhances the recovery of MTX- and PALA-resistant mouse 3T6 cell clones but has little or no effect on drug-resistant colony recovery in the V79 Chinese hamster cell line. The possibility that the increase in accumulation of cells in G1 might permit the rescue of an increased proportion of cells due to the release of purines and pyrimidines from dying cells is discussed. Such rescue should occur irrespective of whether or not the cell line has the ability to amplify its target genes.