title: A genetic effect of altered gravity: mutations induced by simulated hypogravity and hypergravity in microsatellite sequences of human tumor cells.
abstract: To determine the possible genetic effects of gravity alterations, we analyzed mutation induction in microsatellite sequences of human tumor cells treated with simulated hypogravity provided by a clinostat or hypergravity by a centrifuge. Microsatellite mutations were detected as changes in the size of polymerase chain reaction (PCR)-amplified allelic markers. The frequencies of mutant clones in cultures treated with simulated hypogravity for 24 or 48 h were almost the same as those of controls, but after 72 h of treatment, the mutant frequencies had increased significantly in all three microsatellite loci examined. Significantly higher mutant frequencies were similarly detected in cultures treated for 72 h with a hypergravity condition as low as 18xg, but not detected in 24 or 48 h treated cultures. These findings clearly show that gravity alterations that last for 3 days can induce microsatellite mutations in human cells. A genetic effect of gravity change, therefore, is established for the first time. Moreover, high frequencies of microsatellite mutations were induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) which activates protein kinase C-mediated signal transduction pathways and causes genetic instability. These findings suggest that gravity change induces microsatellite mutations by modulating the pattern of gene expression involved in signal transduction pathways.
mesh_terms: D017931:DNA Primers; D018470:Gravity, Altered; D006801:Humans; D018895:Microsatellite Repeats / Q000187:drug effects / Q000235:genetics* / Q000528:radiation effects; D009154:Mutation; D016133:Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D014965:X-Rays