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THE CYTOSKELETON AND CELL CYCLE IN SPACEFLIGHT.  M. Hughes-Fulford 1,2 and Jason Hatton.2 Dept of Medicine, Univ of California, San Francisco and 2NCIRE, San Francisco, CA 94121

   A multitude of mammalian cells have been grown in microgravity including Ros 17/2.8, MC3T3-E1, MG-63, hFOB and primary chicken calvaria. Changes in cytoskeleton and extracellular matrix (ECM) have been noted in many of these studies. Investigators have noted changes in shape of cells exposed to as little as 20 seconds of microgravity in parabolic flight. We found that quiescent osteoblasts activated by sera in microgravity had a significant 60% reduction in growth (p<0.001) and a collapse of the osteoblast actin cytoskeleton after 4 days in microgravity.  Studies on STS-76, 81 and 84 confirmed the collapse of the actin cytoskeleton in cells grown in microgravity conditions at 24 hours, however space flown cells under 1g conditions maintained normal actin cytoskeleton. The changes seen in the cytoskeleton are probably not due to alterations in fibronectin message or protein synthesis since no changes have been noted in microgravity.  Actin and microtubule cytoskeletal modifications in microgravity, suggesting a common root cause for the change in cell architecture. The inability of the 0g grown osteoblast to respond to sera activation suggests that there is a major alteration in anabolic signal transduction under microgravity conditions, most probably through the growth factor receptors and/or the associated kinase pathways that are connected to the cytoskeleton. Cell cycle is dependent on the cytoskeleton. Alterations in cytoskeletal structure can block cell growth either in G1 (F-actin microfilament collapse), or in G2/M (inhibition of microtubule polymerization during G2/M-phase). We therefore hypothesize that microgravity would inhibit growth in either G1, or G2/M. (NAG-1286)