SYNERGISTIC CYTOTOXIC EFFECTS OF ETHER PHOSPHOLIPID ANALOGS AND IONIZING-RADIATION IN HUMAN CARCINOMA-CELLS

Background and purpose: There is growing evidence in recent years that the antiproliferative effects of ionizing radiation may not be exclus ively mediated via DNA damage but also by interactions and alterations of cell membrane associated processes. Here, we tested the hypothesis that membrane active cytotoxic ether lipids and analogues may interac t with ionizing radiation, enhancing its antiproliferative effects. Ma terials and methods: The two epithelial tumor cell lines HTB 43 and KB , and the ether lipid resistant subline KBr were treated by a combinat ion of radiation and ether lipids. Cytotoxic effects were measured by colony forming assays and the effects on membrane phospholipids were d etermined by quantitative thin-layer chromatography of cell lipid extr acts. Results: We present evidence that some ether lipids show supra-a dditive cytotoxic effects with ionizing radiation. These effects seem to depend on the same structural properties of ether lipids that deter mine their intrinsic cytostatic and cytotoxic activity. Identical grow th inhibitory results were achieved when cells were treated before, or 30 min after irradiation. Analysis of major membrane phospholipids re vealed no statistically significant differences of phospholipid distri bution pattern in cells exposed to both treatment modalities. Conclusi on: Our data indicate that changes of overall membrane phospholipid co mposition do not seem to be the mechanism of synergistic antiprolifera tive activity of ether lipids and ionizing radiation. (C) 1997 Elsevie r Science Ireland Ltd.