EFFECTS OF THE GLUCOSPHINGOLIPID SYNTHESIS INHIBITOR, PDMP, ON LYSOSOMES IN CULTURED-CELLS

The glucosphingolipid synthesis inhibitor, 1-phenyl-2-decanoylamino-3- morpholino-1-propanol (PDMP) has a wide range of effects on cell physi ology and morphology. Here, we studied the effects of high concentrati ons of PDMP on cells in culture and found that fluorescent analogs of PDMP targeted to the lysosomes of Chinese hamster ovary (CHO) cells. O vernight incubation of the cells in the presence of drug induced enlar gement (''vacuolization'') of the lysosomes. PDMP was toxic at high co ncentrations (> 30 mu M); this finding was used to select CHO cells th at exhibited increased resistance to PDMP (PDMP(R) cells). The PDMP(R) cells were similar to 2-fold more resistant to PDMP than the parental cells (CHO-P). PDMP(R) cells were resistant to a number of other drug s that are also lipophilic and possess a titratable amino group. The m ultidrug resistance exhibited by the PDMP(R) cells was distinct from t hat observed in cells (MDR cells) that overproduce the plasma membrane drug pump, P-glycoprotein. In addition, MDR cells were extremely sens itive to PDMP.