In the last 20 years usage of radiation during medical diagnostic procedures and treatment protocols have largely increased. This radiation causes DNA damage to human cells. However, the sensitivity to radiation varies between individuals. This individual variability is even observed at the gene expression level. The way cells deal with exposure to radiation depends on the amount that radiation induced genes are induced or repressed. This change in expression of the gene, determines the cellular response (Smirnov et al, 2009).
Smirnov et al (2009) had accomplished prior analysis of chromosomal regions and gene variants that can change gene expression levels. They then extended their study to include the genetic mapping of regulatory elements that influence radiation induced changes in gene expression.
For their study, Smirnov et al (2009) used immortalized B cells extracted from members of known pedigrees. The cells were harvested before irradiation and after 2 and 6 hours of irradiation. Microarrays were used to analyse the gene expression levels of 10,174 genes. This number included 3,280 ‘ionizing radiation response’ genes that were harvested from the 2 and 6 hour batches. These genes showed a change in gene expression level compared to the expression at baseline levels.
With this, DNA variants that influence the gene expression levels were identified via genetic linkages and association analyses. The results of these permitted Smirnov et al (2009) to generate a general regulatory landscape of gene expression response to irradiation. It was noticed that almost all of the radiation induced expression phenotypes are regulated by trans-acting factors, while only 1% were cis regulated. Usually, interchromosomal interactions produce a ‘cis regulatory’ DNA that acts ona different chromosome (Rockman & Kruglyak, 2006). The trans regulators can coordinate the cell’s responses since it can influence the expression of certain genes. Since this similar to the results found in C. elegans and yeast, Smirnov et al (2009) suggest that this phenomenon may be found in different organisms.
Regulators and regulatory genes have also been identified by combining the research’s results of genetic mapping and molecular validation studies. This identification has uncovered polymorphic regulators of gene expression response to radiation (Smirnov et al, 2009).
In conclusion, the results of this research have obvious revolutionary clinical applications. The regulatory variants that were identified by Smirnov et al (2009) will be useful in genetically predicting an individual’s sensitivity to radiation for clinical procedures. Also, this will help develop radiosensitizers that increases tumour sensitivity to radiation. With the knowledge of a patient’s sensitivity to radiation and the methodology to sensitize tumours to radiation, new processes of radiotherapy can be generated to aid clinical practices (Smirnov et al, 2009).
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References:
Rockman, M.V & Kruglyak, L. (2006). Genetics of global gene expression. Nature. 7, 862 – 872.
Smirnov, D.A, Morley, M, Shin, E, Spielman, R.S & Cheung, V.G. (2009). Genetic analysis of radiation-induced changes in human gene expression. Nature.
