Monitoring human radiation exposure by gene expression profiling: possibilities and pitfalls.
Advances in high throughput analysis of mRNA expression have made it possible to establish gene expression profiles for different cells, tissues, diseases and exposure states. For instance, recent studies have demonstrated the utility of such an approach to classify sub-types of cancers with more detail than was previously possible. In addition, gene expression studies of ionizing radiation exposure both in vitro and in vivo are affording insight into the molecular mechanisms of mammalian radiation response. We have demonstrated that radiation expression profiles are a good predictor of p53 function in cell lines, and such profiles also indicate a major role for p53-regulated genes in the in vivo radiation response. Gene expression can be a sensitive indicator of radiation response as we have shown linear dose-responses for induction of several genes down to doses as low as 2 cGy. As profiles are established from radiation studies, it is hoped that they may be useful for identifying individuals with specific exposures or predisposition to negative outcome of exposure. Although this technology holds great promise, some obstacles remain to be overcome before it can be successfully applied to population studies.
Amundson
Sally A
SA
National Cancer Institute, NIH, 37 Convent Drive, Bldg. 37, Rm. 6144, Bethesda, MD 20892, USA. amundson@mail.nih.gov
Fornace
Albert J
AJ
D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics / Q000528:radiation effects; D004247:DNA / Q000528:radiation effects; D005720:Gamma Rays; D015870:Gene Expression / Q000528:radiation effects; D020869:Gene Expression Profiling / Q000379:methods*; D005786:Gene Expression Regulation / Q000528:radiation effects*; D016158:Genes, p53 / Q000528:radiation effects; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism / Q000528:radiation effects; D032446:Myoblasts / Q000378:metabolism / Q000528:radiation effects; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D011874:Radiometry / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013223:Statistics as Topic
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D004247:DNA