Lack of consensus gene expression changes associated with radiation-induced chromosomal instability.
The relatively high frequency with which ionizing radiation induces genomic instability suggests that a gene mutation occurring after irradiation is an unlikely cause of the phenotype. To search for mechanism(s) of initiation and perpetuation of this instability phenotype, gene expression profiles of clones exhibiting delayed chromosomal instability were analyzed. Microarray analysis using two pools of isogenic radiation-induced chromosomally unstable clones compared to an irradiated but chromosomally stable clone uncovered a set of 68 differentially expressed genes using two methods of analysis. Unexpectedly, all 68 genes were under-expressed relative to the chromosomally stable reference clone. Further analysis of the candidates placed the differentially expressed genes into pathways implicating differential MAP kinase signaling, ubiquitin/proteasome function, DNA repair, cell cycle control, lipid signaling, nucleotide metabolism, and other potentially disrupted pathways. Validation studies using northern and western blotting, and functional assays concluded that although differences in some of these pathways exist, no single gene or molecular pathway was found to be differentially regulated in all of the chromosomally unstable clones tested. Inferred from these data is that there are multiple potential molecular pathways and/or events that maintain the unstable phenotype, and no single expression pattern is linked to instability in the unstable clones analyzed.
Snyder
Andrew R
AR
Molecular and Cell Biology Graduate Program, Bressler Research Building, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201, USA.
Morgan
William F
WF
D000818:Animals; D016466:CHO Cells; D043171:Chromosomal Instability / Q000528:radiation effects*; D006224:Cricetinae / Q000235:genetics*; D004260:DNA Repair; D005434:Flow Cytometry; D005784:Gene Amplification; D015870:Gene Expression / Q000528:radiation effects*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis