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Abstract

Exposure to ionizing radiation occurs from natural sources (e.g. cosmic or terrestrial radiation) or man-made sources (e.g. radiation used in diagnosis and radiotherapy). Ionizing radiation being used in diagnostic procedures (X-ray or computed tomography) can increase the risk of development of ionizing radiation induced cancer even at low doses. A better understanding of biological effects and cellular responses to ionizing radiation will lead to efficient use in radiotherapy and better protection. Up to now, it is not clear to what extent the different NF-�ºB target genes are activated in response to different doses and qualities of ionizing radiation. Therefore, the effect of heavy ions of a broad LET range (â�¼ 0.3 - 9674 keV/�¼m) on cellular survival and activation of NF-�ºB were investigated. The biological relevance of the recently discovered LET dependency of NF-�ºB activation is also unknown, especially the resulting profile of NF-�ºB target gene expression. This study clearly demonstrates that NF-�ºB activation and NF-�ºB-dependent gene expression by heavy ions are highest in the LET range ofâ�¼50-200 keV/�¼m. The up-regulated chemokines and cytokines (CXCL1, CXCL2, CXCL10, IL-8 and TNF) might be important for cell-cell communication among hit as well as unhit cells (bystander effect). Hence, the expression profile was determined in this work. The results clearly show the role of LET in modulating radiation induced NF-�ºB activation and NF-�ºB dependent gene expression by ionizing radiation of different LET.

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