Relationship between cell size and specific thrombopoietin productivity in chinese hamster ovary cells during dihydrofolate reductase-mediated gene amplification

When parental Chinese hamster ovary (CHO) cell clones that are capable of producing thrombopoietin (TPO) were subjected to high methotrexate (MTX) concentrations, clonal variations in cell growth were apparent. In the clones that had no significant enhancement in specific TPO productivity (q ^sub Tpo^) when a higher level of MTX was administered, their growth was not depressed significantly nor their cell size changed significantly. On the other hand, those clones that showed a significant enhancement inq ^sub Tpo^ at higher a MTX dosage, cell growth was depressed initially but recovered during successive sub-cultures. Furthermore, their cell size increased, which suggested that changes in cell size may be indicative of an enhancedq ^sub Tpo^. When the enhancement of theq ^sub Tpo^ of 9 clones after a high MTX dosage was plotted against the extent of the increase of their size, there was a linear correlation (r ^sup 2^=0.80,P