Abstract
HiCEP (high-coverage expression profiling) enables to detect any altered gene expression among 60-70% of all the actually transcribed genes in any eukaryotic cells and tissues. We previously applied it to a primary culture of normal human fibroblasts and observed gene expression responding to X-ray at the very low dose (10 mGy). As the result of screening for approximately 23,000 transcripts, we have identified a set of CXC chemokines up-regulated by the 10 mGy X-rays in the normal human fibroblasts. Those genes have hardly been expected from the previous studies using the higher (>100 mGy) dose of radiations. Our observation indicated that different molecular mechanisms are involved in the response to ionizing radiation with different doses /dose rates, and suggested that different cellular responses are induced by ionizing radiation with different LET. Accelerated heavy ion particle (high LET) provides promising effects for radiotherapy of a certain type of malignancy, however, the molecular bases of its advantage to gamma rays is not fully understood. In this time, we applied our new expression assay (HiCEP) to the normal human fibroblasts (HFL III) irradiated with a high-LET which was generated by HiMAC in our institute. More than 40 genes were found to be unregulated in the irradiated cells by >3 folds within 4 hrs post-irradiation of carbon ion at 2Gy (~70 keV/micro m). Those included the DNA damage-inducible genes (CDKN1A, MDM2, Gadd45), and also some unexpected genes, both predicted and unpredicted from the current public databases.
