Modulation of cell cycle progression and of antibody production in mouse hybridomas by a nucleotide analogue

The nucleotide analogue 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG) has bee n identified as a powerful antiproliferative substance when acting on hybri doma cells. In the range of 10 nM to 100 nM concentrations this agent reduc es cell growth rate, while its apoptosis-inducing activity is marginal. Mar ked induction of apoptosis can be observed at micromolar and higher order c oncentrations. In PMEG-supplemented media the cell cycle progression is per turbed, the flow-cytometric DNA profile shows a higher proportion of cells in the S and G(2)/M phases of the cell cycle. Concomitantly with the reduct ion of the growth rate, the specific monoclonal antibody production rate ma y rise by 20-27%. Addition of PMEG at the end of the exponential phase of a batch culture results in an enhancement of the final monoclonal antibody c oncentration.