RELATIONSHIP OF CELL-SURVIVAL, DRUG DOSE, AND DRUG UPTAKE AFTER -OCTADECYL-2-O-METHYL-RAC-GLYCERO-3-PHOSPHOCHOLINE TREATMENT

The mechanisms that govern the activity and the factors that control t he anticancer activity of synthetic ether lipids have not been fully e lucidated. In this study, three factors were studied in relationship t o cell survival after treatment with -octadecyl-2-O-methyl-rac-glycero -3-phosphocholine (ET-18-OCH3): (1) exposure dose, (2) drug uptake, an d (3) cell density and cell-cycle distribution. In BG-1 human ovarian carcinoma cells, cell survival was an exponential function of exposure dose and was dependent on drug concentration. Drug uptake was depende nt on the concentration of ET-18-OCH3, whereas the reduction in cell s urvival was directly related to the uptake of drug only in the first d ecade of cell kill. When the quantity of cells per flask was tripled f rom 4 to 12x10(6) cells, ET-18-OCH3 failed to induce a G(2) block. Fur thermore, the cell kill induced by a 72-h exposure to 2 mu M ET-18-OCH 3 was decreased by a factor of 2 when the cell density increased. Ther efore, exposure dose and cell density are important parameters in dete rmining the cell kill induced by ET-18-OCH3.