Prolonged weightlessness affects promyelocytic multidrug resistance.
An immortalized promyelocytic cell line was studied to detect how doxorubicin uptake is affected by microgravity. The purpose of this experiment was to identify the effect that microgravity may have on multidrug resistance in leukocytes. HL60 cells and HL60 cells resistant to anthracycline (HL60/AR) were grown in RPMI and 10% FBS. Upon reaching orbit in the Space Shuttle Endeavour, the cells were robotically mixed with doxorubicin. Three days after mixing, cells were fixed with paraformaldehyde/glutaraldehyde. Ground control experiments were conducted concurrently using a robot identical to the one used on the Shuttle. Fixed cells were analyzed within 2 weeks of launch. Confocal micrographs identified changes in cell structure (transmittance), drug distribution (fluorescence), and microtubule polymerization (fluorescence). Flight cells showed a lack of cytoskeletal polymerization resulting in an overall amorphic globular shape. Doxorubicin distribution in ground cells included a large numbers of vesicles relative to flight cells. There was a greater amount of doxorubicin present in flight cells (85% +/- 9.7) than in ground control cells (43% +/- 26) as determined by image 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 function of P-glycoprotein as a drug efflux pump responsible for multidrug resistance.
Piepmeier
E H
EH
College of Pharmacy, University of Texas at Austin 78712, USA.
Kalns
J E
JE
McIntyre
K M
KM
Lewis
M L
ML
D001692:Biological Transport; D002460:Cell Line; D003599:Cytoskeleton / Q000648:ultrastructure*; D004317:Doxorubicin / Q000378:metabolism* / Q000494:pharmacology; D018432:Drug Resistance, Multiple; D018922:HL-60 Cells / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D018613:Microscopy, Confocal; D013026:Space Flight; D014404:Tubulin / Q000378:metabolism; D014893:Weightlessness
D014404:Tubulin; D004317:Doxorubicin