Risks and Modeling at Low Doses

Sunday, October 16, 2005 3:00 PM-5:00 PM Exhibit Hall

(PP031) Adaptive response of mouse skin epithelial cells to low dose ionizing radiation: induction of NF-kappaB, MnSOD, 14-3-3zeta and cyclin B1.

Ahmed, Kazi*,1, Fan, Ming1, Dong, Shaozhong1, Yu, Cheng-Rong2, Spitz, Douglas3, Li, Jian Jian 1, 1 Division of Molecular Radiobiology, West Lafayette, Indiana, USA2 Laboratory of Immunology, Bethesda, Maryland, USA3 Department of Radiation Oncology, Iowa City, Iowa, USA

ABSTRACT- Gene expression profiles demonstrate that a group of key stress responsive genes are associated with radiation exposure and may contribute to cellular responses to radiation. The present study provides evidence suggesting that the transcription factor NF-kappaB, the mitochondrial antioxidant MnSOD, and cell cycle regulatory elements 14-3-3zeta and Cyclin B1 are specifically induced in mouse skin JB6 P+ cells by exposure to a single low dose of ionizing radiation (0-20 cGy). In contrast to NF-kappaB activation, NF-kappaB subunit p65 protein levels were not altered in irradiated cells, indicating an early response of NF-kappaB to low dose radiation induced stress. Protein levels of MnSOD, 14-3-3zeta and Cyclin B1 were increased as early as 1 h following radiation and were maintained for different time periods after radiation. To further investigate the function of low dose induced signaling proteins, fluorescence-fusion vectors containing full length 14-3-3zeta and Cyclin B1 genes were co-transfected and protein interactions and localization were analyzed in living cells with or without radiation. Compared to the control known interactions between 14-3-3zeta and GADD45beta, interactions between 14-3-3zeta and Cyclin B1 were increased in cells with and without low dose radiation. In addition, the protein complexes containing 14-3-3zeta and Cyclin B1 were found to be translocated into the nucleus after radiation, which contrasts to the complexes of 14-3-3zeta and GADD45beta that stayed in the cytoplasm with and without radiation. Overall, these results demonstrate that a group of pro-survival elements are specifically activated in mouse skin epithelial cells by low dose radiation. Interaction and nuclear translocation of 14-3-3zeta and Cyclin B1 could play a key role in low dose-induced adaptive responses.

Key words: Low dose, adaptive response, signal transduction

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2005 RRS