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Gravisensing, apoptosis, and drug recovery in Taxus cell suspensionsHaploid and diploid cell suspensions of Taxus spp. were examined for their adaptive plasticity in response to simulated microgravity, unit gravity, and hypergravity. Cell suspensions produced the taxane, paclitaxel, (TAXOL (R)), which is useful for the treatment of various cancers. Amyloplasts contributed to taxane ring biosynthesis and to drug release at the cell wall. Drug-producing cells reacted as gravisensing osmotic tensiometers. In stressed cells, amyloplasts docked and fused in clusters to sites on the plasmalemma before taxane discharge into the culture medium. In simulated microgravity and compared to all other treatments, taxane production was reduced nearly 100-fold. The percent paclitaxel of total taxanes remained 3-to 6-fold greater, and biomass doubled. When p53-independent programmed cell death was induced, taxanes were released into the culture medium as free molecules (soluble and insoluble) or bound to membranes, nuclear fragments, xylan residues, and other particulate materials. Unit gravity and especially hypergravity promoted xylogenesis and significant drug overproduction. A model relating families of >touch = (TCH), taxane early response (TER), nuclear cycling, and apoptosis-regulating genes to gravisensing, cell wall modifications, and to taxane recovery accounted for most but not all of the observations.
Document ID
20040120440
Acquisition Source
Johnson Space Center
Document Type
Reprint (Version printed in journal)
Authors
Durzan, D. J.
(University of California Davis, United States)
Date Acquired
August 22, 2013
Publication Date
May 1, 1999
Publication Information
Publication: Gravitational and space biology bulletin : publication of the American Society for Gravitational and Space Biology
Volume: 12
Issue: 2
ISSN: 1089-988X
Subject Category
Aerospace Medicine
Funding Number(s)
CONTRACT_GRANT: NAG9-225
Distribution Limits
Public
Copyright
Other

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