CYTOKINETIC AND MORPHOLOGIC DIFFERENCES IN OVARIAN-CANCER CELLS TREATED WITH ET-18-OCH3 AND THE DNA-INTERACTING AGENT, ETOPOSIDE

New antineoplastic agents with different cytotoxic mechanisms are of i nterest for their ability to overcome resistance to conventional DNA-i nteracting agents. Ether lipids are known to be active against ovarian carcinoma both in vitro and in vivo, and the cell membrane is believe d to be the target of their antitumor activity. In this study we have investigated the different cytokinetic and morphologic responses of hu man ovarian carcinoma cells (BG-1) to one of the ether lipids (ET-18-O CH3) and to etoposide. Etoposide induced a significantly greater G(2)/ M block. However, the proportion of the cycling cell fraction decrease d significantly in cells treated by ET-18-OCH3 and induction of the hy podiploid fraction was strongly correlated with reduction of the cycli ng cell fraction. On the other hand, the hyperdiploid fraction was fou nd to correlate with reduction of the cycling cell fraction in etoposi de treated cells. Despite the significant appearance of the hypodiploi d fraction, apoptosis was not observed by DNA-gel assay. Microscopic s tudy showed that the hyperdiploid fraction represented cells with mult iple nuclei. These observations support the unique lethal effect of ET -18-OCH3 on ovarian carcinoma cells, distinguishing it from the action of a typical DNA-interacting agent. The membrane-targeted ether lipid s deserve consideration for the future chemotherapy of ovarian carcino ma, perhaps in combination with the appropriate DNA-interacting agent.