Activity of etoposide (VP-16) and teniposide (VM-26) in exponential and plateau phase human tumor cell cultures

The effects of etoposide (VP-16) and teniposide (VM-26) have been evaluated in human epidermoid carcinoma cells (A431, ME180 and HEp3) grown as exponential and plateau phase cultures. A significant increase in resistance to both these chemotherapeutic agents was observed in unfed plateau compared with exponential phase cells. The large differences in cell killing could not be explained by cell cycle specific toxicities resulting from variations in the cell cycle distributions. Rather the differences in the treatment efficacies probably reflect the 5- to 15-fold increase in the proportion of quiescent cells measured in the plateau phase cultures. These findings suggest that non-proliferating cells in tumors may be preferentially spared in treatments utilizing VP-16 and VM-26.