Background: To identify differentially expressed genes between parent and radioresistant lung cancer cell lines established by fractionated irradiation.

Materials And Methods: Lung cancer cell lines (A549, NCI-H1650) were irradiated with several fractionation schemes. Clonogenic assays were used to identify radioresistant cell lines. We compared the gene expression profiles on a cDNA microarray.

Results: Four established cell (A549-2G, A549-5G, H1650-2G and H1650-5G) were shown to be radioresistant (p≤0.05). Seventy-two genes were commonly altered in A549-G and 655 genes in H1650-G, compared to their parental cells. Genes in the wingless-type MMTV integration site family (WNT) signaling pathway were the ones most frequently altered in both A549-G and H1650-G cells. Those involved in inflammation; integrin, platelet-derived growth factor (PDGF), interleukin, transforming growth factor-beta (TGFB), epidermal growth factor receptor (EGFR) signaling, were commonly altered in radioresistant H1650 sublines.

Conclusion: The major gene expression changes during irradiation are related to WNT signaling pathway.

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