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(PP353) Persistent genomic instability induced by HZE particle radiation in human mammary epithelial cells.
Sudo, Hiroko*,1, Stampfer, Martha1, Barcellos-Hoff, Mary-Helen*,1, Kronenberg, Amy1, 1 Life Science, Berkeley, CA, United States
ABSTRACT- The carcinogenic risks of radiation exposure represent one of the gravest and most complex issues for astronauts engaging in long duration space flights. Radiation-induced genomic instability may contribute to the incidence of cancer and has been studied in several model systems, but scarce data exist for finite-lifespan human epithelial cells that are a more relevant cell type at risk for the development of solid tumors. Using a human mammary epithelial cell strain (HMEC 184v) which has a normal karyotype and finite life span, we are assessing the importance of radiation-induced genomic instability. Our goal is to test whether densely ionizing heavy-ions are more potent inducers of genomic instability than sparsely ionizing X-rays and whether the immortalization is a requirement for the establishment of genomic instability. HMEC at passage 7 were irradiated with 0-6 Gy of X-rays while holding the cells in G0 phase simulating the in vivo condition. Cell survival decreased exponentially with increasing dose. Genomic instability of the individual surviving colonies was investigated both with centrosome staining by -tubulin antibody and with whole chromosomal painting fluorescent in situ hybridization (WCP-FISH) for chromosomes 1, 2 and 4 to assess non-clonal aberrations within the surviving progeny of irradiated clones. Abnormal centrosome numbers indicate incomplete chromosomal segregation, leading to aneuploidy which is a hallmark of carcinogenesis. 23/26 colonies irradiated with 1-6 Gy X-ray had more than two centrosomes exhibiting centrosome abnormalities with >2 S.D. above the level of control clones (0.63±0.35%, n=8). Defining a dose-response of centrosome abnormalities requires further analysis of more clones particularly at higher doses. WCP-FISH analyses are underway and experiments with heavy ions are about to begin. ±±∼
Key words: genomic instability, mammary epithelial, heavy ion, FISH
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