TRANSPORT MECHANISM OF ANTHRACYCLINE DERIVATIVES IN RAT POLYMORPHONUCLEAR LEUKOCYTES - EFFECT OF SODIUM-FLUORIDE ON PIRARUBICIN UPTAKE

We previously revealed that pirarubicin (THP) was actively taken up by rat polymorphonuclear leukocytes ria a carrier-mediated transport sys tem. In the experiment on the effects of the metabolic inhibitors, rot enone, 2,4-dinitrophenol and sodium cyanide significantly decreased th e THP transport. However, sodium fluoride (NaF) significantly increase d the uptake, and this result is different from that in some reports. Therefore, we examined the action of NaF on THP uptake by the leukocyt es to clarify the discrepancy in the effect of NaF on drug transport. The accelerating effect of 30 mM NaF on the THP uptake by the cells ha d an optimum period of action (15-20 min), and was concentration-depen dent (5-30 mM). Thirty nM potassium fluoride, as,veil as NaF, increase d the uptake amount. On the other hand, NaF (5-30 mM) dose-dependently decreased the ATP content in these cells. Additionally, the viable ce lls in the reaction suspension decreased by about 40% after incubation with 30 mM NaF for 15 min. Observing these leukocytes treated with Na F by optical microscopy, swelling of the cell and an alteration of the nuclei form occurred. On the basis of these results, we speculated th at the increased THP transport in polymorphonuclear leukocytes by NaF, probably F-, might be due, at least in part, to an alteration of the morphological form.