Interaction of melphalan and dexamethasone in a human myeloma cell line

The effects of a combination of melphalan and dexamethasone on cell growth, cell cycle flow, cell loss and DNA cross-links were studied on a myeloma cell line (RPMI 8226). At low concentrations melphalan reduced the cell growth by prolonging the S and G2 stages. Steroid sensitivity of the cell line was characterized by dose-dependent inhibition of cell growth after exposure of up to 1 micron dexamethasone with no cell loss found even at 10-fold saturation concentration. Dexamethasone induced prolongation of all cell cycle phases without any preferences. In combined treatment with melphalan and dexamethasone, inhibition of cell growth was found after 24 h followed by cell loss after 48 h. This cell loss was obtained with concentrations of the drugs which by themselves are only growth inhibitory. Calculation of cell flow showed that cell loss is a delayed process occurring after the cells have left the G1 phase. By alkaline elution it was found that dexamethasone treatment caused an increase in melphalan-induced DNA interstrand crosslinks.