TETRAPHENYLPHOSPHONIUM CHLORIDE-INDUCED MR-VISIBLE LIPID-ACCUMULATIONIN A MALIGNANT HUMAN BREAST CELL-LINE

The effect of the cationic lipophilic phosphonium salt tetraphenylphos phonium chloride (TPP) on a human malignant breast cell line, DU4475, was monitored with proton nuclear magnetic resonance (H-1 MRS). TPP ca used a dose- and time-dependent increase in resonances arising from MR -visible lipid as measured by the CH2/CH3 ratio in the 1-dimensional H -1 MR spectrum. Two-dimensional MRS identified increases in the glycer ophosphocholine/lysine cross-peak ratio and corresponding decreases in the phosphocholine/lysine ratio in a dose-dependent fash ion in TP P- treated cells. Lipid metabolic changes are discussed in the light of o ther MR experiments, and the data indicate that accumulation of MR-vis ible lipids may arise from the rearrangement of phospholipids accompan ying mitochondrial destruction or from the catabolism of phospholipids associated with early events in the cytotoxic process. (C) 1996 Wiley -Liss, Inc.