ROLE OF METABOLIC WASTE PRODUCTS IN THE CONTROL OF CELL-PROLIFERATION AND ANTIBODY-PRODUCTION BY MOUSE HYBRIDOMA CELLS

In order to determine the factors limiting the proliferation and productivity of mouse hybridoma cells in batch/fed-batch cultures, we tested the influence of various environmental parameters on the growth of a model cell line VO 208. We observed that, among the major metabolic waste products, ammonium ions at concentrations superior to that present in the medium at die end of a batch culture do not exert a significant toxic effect on cell growth, whereas in contrast acid is cytotoxic at concentrations reached in cultures. Feeding of fructose instead of glucose during the stationary phase of the culture markedly prolongs die life span of the culture and enhances the antibody secretion accordingly. However, we failed to observe a satisfactory proliferation pattern in cultures grown in a glucose-free fructose-supplemented medium. We also noted that vitamin supply may be limiting in fed-batch cultures. It thus appears that thorough examination of the cell metabolic needs allows the designing of a culture regimen which significantly improves cell growth and secretion.