Dose-dependent expression changes of early response genes to ionizing radiation in human lymphoblastoid cells.
The sensitivity of cancer cells as well as normal cells in response to ionizing radiation (IR) is believed to be associated with the early inducible expression of specific genes. Using cDNA microarray technology, here we explored and compared the global transcriptional changes in human lymphoblastoid AHH-1 cells irradiated with 0.05-, 0.2-, 0.5-, 2.0- and 10-Gy doses of gamma-rays 4 h after exposure. A dose as low as 0.05 Gy was efficient in inducing a transcriptional response including the up-regulation of 25 genes, some of which are involved in signal transduction pathways, e.g. BMPR2, GPR124, MAPK8IP2 and AGGF1, and the down-regulation of 18 genes. Expression of some genes was altered only at a specific dose. Most importantly, we discovered a number of radiation-response genes, e.g. DNA repair gene XPC, tumor protein p53 inducible protein 3 gene (TP53I3), immediate early response 5 gene, whose transcriptional levels were increased or depressed by IR in a dose-dependent trend within the dose range 0.05-10 Gy. The dose-dependent induced expression of TP53I3 and XPC was confirmed by Northern blot analyses. Using quantitative real-time PCR, we further confirmed that XPC gene induction was dose dependent as well as time dependent, reaching a peak 4 h post-2 Gy and 10 h post-0.05 Gy. The maximum induced expression level of the XPC gene was higher after 2 Gy (3.2-fold) than 0.05 Gy (1.93-fold). The identification of these radiation-inducible genes, especially those exhibiting a dose-dependent response, not only expands our knowledge of the mechanisms underlying the diverse biological effects induced by IR, but provides candidates for developing novel biomarkers of radiation injury.
Long
Xian-Hui
XH
Department of Radiation Toxicology and Oncology, Beijing Institute of Radiation Medicine, Beijing 100850, P.R. China.
Zhao
Zeng-Qiang
ZQ
He
Xing-Peng
XP
Wang
Hui-Ping
HP
Xu
Qin-Zhi
QZ
An
Jing
J
Bai
Bei
B
Sui
Jian-Li
JL
Zhou
Ping-Kun
PK
D045744:Cell Line, Tumor; D004260:DNA Repair / Q000235:genetics / Q000528:radiation effects*; D004268:DNA-Binding Proteins / Q000235:genetics; D004307:Dose-Response Relationship, Radiation; D015536:Down-Regulation; D005720:Gamma Rays; D015870:Gene Expression / Q000528:radiation effects*; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D008223:Lymphoma / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D015533:Transcriptional Activation; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D004268:DNA-Binding Proteins; D016159:Tumor Suppressor Protein p53; C086984:XPC protein, human