The Expression Changes Of Inflammation-related Genes That Respond To X-ray In Human Peripheral Blood

ObjectiveWe screened inflammation-related genes that respond to ionizing radiation toanalysis the differences of expression profile, dose-dependent response,time-dependent response and the expression levels of a normal population, as well asto explore the molecular mechanism of inflammatory reaction induced by ionizingradiation and the feasibility of specific gene expression patterns as radiationbiodosimeter．Materials and Methods1. Expression profile of inflammation-related genes after X-ray irradiation.Human peripheral blood samples (one female) were irradiated with0,0.5,3and10Gy X-ray, and quantitative reverse transcription-polymerase chain reaction (QPCR)array analysis was performed to investigate the expression changes of84inflammation-related genes at mRNA level after24h incubation.2. Dose-dependent and time-dependent response of inflammation-related geneswith radiation-induced expression changes. Human peripheral blood samples wereirradiated with0,1,3,5,8,10and12Gy X-ray, and real-time fluorescentquantitative reverse transcription polymerase chain reaction (Q-RT-PCR) analysiswas performed to investigate the expression level of CD40LG, BIRC2, IFNG,TNFSF4, CCL2and CCL7mRNA after6,12and24h incubation.3. Relative expression of inflammation-related genes mRNA associated withradiation response in the peripheral blood of a normal population. Q-RT-PCR analysiswas performed to evaluate the relative expression levels of TNFSF4, CCL2andCCL7mRNA of a normal population.Results1. Expression profile of inflammation-related genes after X-ray irradiation. Totalof62radiation responsive genes were screened out with QPCR array. At the low doseof radiation (0.5Gy),9and19unique genes were shown to be up-anddown-regulated, respectively. Following an increased exposure to the3Gy dose,8 unique genes were up-regulated, while19genes were down-regulated. Likewise, weidentified that48different genes were supposed to significant differentially expressedgenes after10Gy irradiation, and out of these transcripts, genes up-regulated onlyreached one third (16genes).31of these genes were significantly altered only at aspecific dose and a total of10genes were significantly expressed at all three doses.2. Dose-dependent and time-dependent response of inflammation-related geneswith radiation-induced expression changes. The relative expression levels of CD40LG,BIRC2, IFNG, CCL2and CCL7were independent of radiation dose and incubationtime post-irradiation (P>0.05); Moreover, the relative expression level of TNFSF4mRNA exhibited a dose-dependent response across a wide range of doses (0~12Gy)(F=5.765, P=0.013), and the correlation between radiation dose and the relativeexpression level of TNFSF4mRNA at6h or12h was better than that of24hfollowing exposure. Though there was a trend of up-regulation with the increasingincubation time, this held true was independent of incubation time post-irradiation (P>0.05).3. Expression levels of inflammation-related genes associated with radiationresponse in the peripheral blood of a normal population. The relative expressionlevels of TNFSF4, CCL2and CCL7mRNA in the peripheral blood of a normalpopulation were not significantly related to age and gender.Conclusion1. We have identified62inflammation-related genes with radiation-inducedexpression changes in human peripheral blood cells.35of these genes were known tobe associated with radiation response, such as TNFSF4, but others were novel.2. The expression levels of TNFSF4mRNA exhibited a dose-dependentresponse across a wide range of doses. These results suggest that TNFSF4can beconsidered as a candidate gene so as to develop and construct into a newbiodosimeter.