Apoptosis and down-regulated expression of mitochondrial DNA genes in A549 cells induced by X-ray irradiation

Objective: To investigate the apoptotic effect and differential expression of mitochondrial DNA(mtDNA) genes in A549 human lung adenocarcinoma at different doses of X-ray irradiation. Methods: A549 cells were irradiated with 8 MV X rays at the absorbed doses of 2,4,6 or 8 Gy, and then cultured for 24 h. Cell proliferation was detected by MTT assay. Cell cycle distribution and apoptotic rates were determined by flow cytometry (FCM). The apoptotic morphology was observed by transmission electron microscope (TEM). The differential expression of mtDNA genes were detected with mtDNA oligonucleotide microarray. Results: The proliferation of A549 cells was inhibited by X irradiation, especially at 4 Gy. Dose-dependent apoptosis and cell percentage increase of G2/M phase were displayed, while the apoptotic morphological characters were observed at 4 Gy group. Down-regulation of Expression of 3 tRNA genes, 2 tRNA genes and 4 mRNA genes, 6 tRNA genes and 1 rRNA gene, 2 tRNA genes, which were all encoded by mtDNA, were identified at groups 2,4,6 and 8 Gy, respectively. Conclusions: After exposure to X-ray, proliferative inhibition and apoptosis, as well as down- regulated expression of mitochondrial DNA genes were observed in A549 cells and 4 Gy may be regarded as an effective and safe dose in vitro. (authors)