PROLONGED WEIGHTLESSNESS AFFECTS PROMYELOCYTIC MULTIDRUG-RESISTANCE

An immortalized promyelocytic cell line was studied to detect how doxo rubicin uptake is affected by microgravity, The purpose of this experi ment was to identify the effect that microgravity may have on multidru g resistance in leukocytes. HL60 cells and HL60 cells resistant to ant hracycline (HL60/AR) were grown in RPMI and 10% FBS, Upon reaching orb it in the Space Shuttle Endeavour, the cells were robotically mixed wi th doxorubicin. Three days after mixing, cells were fixed with parafor maldehyde/glutaraldehyde. Ground control experiments were conducted co ncurrently using a robot identical to the one used on the Shuttle. Fix ed cells were analyzed within 2 weeks of launch. Confocal micro graphs identified changes in cell structure (transmittance), drug distributi on (fluorescence), and microtubule polymerization (fluorescence). Flig ht cells showed a lack of cytoskeletal polymerization resulting in an overall amorphic globular shape. Doxorubicin distribution in ground ce lls included a large numbers of vesicles relative to flight cells, The re was a greater amount of doxorubicin present in flight cells (85% +/ - 9.7) than in ground control cells (43% +/- 26) as determined by imag e analysis. Differences in microtubule formation between flight cells and ground cells could be partially responsible for the differences in drug distribution. Cytoskeletal interactions are critical to the func tion of P-glycoprotein as a drug efflux pump responsible for multidrug resistance. (C) 1997 Academic Press.