Melphalan resistance in RPMI8226 cells is accompanied by increased S-phase progression and reduced G2/M arrest.

<p>Cell growth rate (A) and cell cycle distribution (B) of sensitive (8226) and resistant (LR5) cells exposed or non-exposed to 2.5 µM Melphalan. (A) Exposure to 2.5 µM Melphalan greatly reduced the proliferation of the sensitive cells, while a minor effect upon the proliferation of resistant cells was observed. (B) Flow cytometric analysis of cell cycle phases shows that 2.5 µM Melphalan caused delayed S-phase progression in sensitive cells followed by G2/M arrest. Conversely, progression throughout S-phase was less affected in the resistant cells exposed to Melphalan. Moreover, the resistant cells were able to overcome the G2/M arrest induced by Melphalan and re-enter the cell cycle. Per cent cells in each of the cell cycle phases are indicated above the histograms. The fraction of cells in subG1 is indicated, but not illustrated in the gated histograms.