This research project is an integrated study of the effects of alkylphospholipids (ALP) and glucocorticoid steroid dexamethasone on cell lines derived from malignant tumors. Since such cells, particularly those originating from lymphoid tissue, frequently become refractory to steroid chemotherapy, it will be the purpose of this study to overcome such resistance through the combined use of glucocorticoids and ALP, two types of antitumor compounds which destroy cells by interfering with the structural and biochemical integrity of the cellular membranes. In spite of the similar method of cell killing, the primary actions of glucocorticoids and ALP are different. Glucocorticoids, in combination with specific receptors, interact with the nuclear elements while ALP act directly at the cell membrane. Nevertheless both types of compounds, when used in low concentrations, can bring about an expression of differentiation markers in malignant cells. The hypothesis to be tested proposes that the combined use of glucocorticoids and ALP will cause amplification of the differentiation process. This study will provide an important contribution to the development of new modalities in cancer chemotherapy based on the induction of differentiation rather than on selective killing of neoplastic cells. This methods to be used include growth assays for the combined effects of dexamethasone and ALP, biochemical determination of changes in cell lipid composition (TLC and HPLC), radioisotope use and fluorescence-activated flow cytometry.
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