Microsatellite mutations in human tumor cells induced by altered gravity conditions including space flight

M Ikenaga, PhDa,b, ZB Han, MD, PhDa, T Kato, PhDa, K Nishizawa, PhDc, K Ishizaki, PhDc

a Radiation Biology Center, Kyoto University, Kyoto, Japan, b Kansai Gaidai University, Hirakata-shi, Osaka, Japan, c Aichi Cancer Center Research Institute, Nagoya, Japan

AIM: Space environment is characterized by microgravity and space radiation. Several studies have suggested that gravity alterations may induce genomic instability through modulation of signal transduction pathways. Therefore, it is imperative to clarify possible genetic effects of microgravity in humans. For this, we analyzed mutations in cultured human cells induced by artificial gravity changes including real microgravity during space flight. METHODS: Mismatch repair-deficient human tumor HCT116 cells were treated with either hypergravity provided by a centrifuge or simulated hypogravity provided by a clinostat. Then, many single cell clones were isolated, microsatellite sequences in each cell clone were amplified by PCR, and microsatellite mutations were detected as changes in the length of PCR fragments. For Space Shuttle experiments, mutations were similarly analyzed using HCT116 cells returned from 9-day space flight. RESULTS: The frequencies of microsatellite mutations in cultures treated for 72 h with hypergravity were significantly higher than those of controls. Similarly, significantly higher mutant frequencies were detected in cultures treated for 72 h with clinorotation. In contrast, the frequencies of microsatellite mutations in cultures grown for 9 days under microgravity in space were similar to those of ground control samples grown in the identical cell culture hardware. CONCLUSION: The results of experiments on the ground clearly showed that altered gravity can induce microsatellite mutations in human cells. However, under the present space flight conditions, neither microgravity nor space radiation induced excess mutations in human cells. Possible reasons for the apparently discrepant findings will be discussed.

KEY WORDS: Mismatch repair, Genomic instability, Microsatellite sequences, Microgravity.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Chromosomal Aberrations.