Analysis of Gene Expression in Normal and Cancer Cells Exposed to γ‐Radiation

Abstract

The expression of many genes is modulated after exposure to ionizing radiation. Identification of specific genes may allow the determination of pathways important in radiation responses. We previously identified modulation of the expression of several genes in response to ionizing radiation treatment. In the present study, we monitored the expression of RGS1, CC3, THBS1, vWF, MADH7, and a novel gene encoding a secreted protein in irradiated Jurkat, TK6, HeLa, and HFL1 cells. The RGS1 is involved in G-protein signaling pathway, CC3 belongs to the complement system, THBS1 is a component of the extracellular matrix, vWF takes part in blood coagulation, and MADH7 is a member of the TGF-β signal transduction pathway. Our objective was to find similarities and differences in the expression of these genes in ionizing radiation-exposed diverse cell types. RGS1 was downregulated in Jurkat cells but was upregulated in TK6 and HFL1 cells. The expression of CC3 was repressed in Jurkat and HFL1 cells but was induced in TK6 and HeLa cells. THBS1 was downregulated in irradiated TK6 and HFL1 cells. vWF was induced in radiation-exposed HeLa cells, but its expression was downregulated in Jurkat cells. The expression of MADH7 was induced in all the cell types examined. These results indicate cell specific modulation of gene expression and suggest the involvement of different pathways in cellular response to radiation treatment in different cells.

The Cellular and Molecular Carcinogenic Effects of Radon Exposure: A Review

“…However, a range of effects have been observed following low-LET irradiation including alterations in gene expression [207], microRNA modulation following chronic and acute exposures [208], differential gene expression between irradiation and bystander cells [209], transcriptional modification of mitochondrial genes [210] and a suggestion that relative levels in the expression of mRNA in blood lymphocytes may provide a biomarker of exposure [211], highlighting the importance of genomic investigations when studying the biological outcomes of radiation exposure.…”

Identification of radiation-induced microRNA transcriptome by next-generation massively parallel sequencing

“…The complexity of the response to IR is evidenced by the alterations in the expression of a large number of genes [9]. The modulation of radiation-induced genes depends upon the cell types, suggesting the activation of different pathways in different cells [10]. The mechanism(s) behind the large scale genome-wide responses in gene expression are not yet fully explored.…”

Molecular markers for prediction of risk of radiation-related injury to normal tissue

“…51 Chaudhry et al monitored radiation induced alterations on the expression of 6 genes including RGS1 (involved in the G-protein signalling pathway), CC3 (from the complement system), THBS1 (an extracellular matrix component), vWF (involved in blood coagulation), MADH7 (member of the TGF-b signal transduction pathway), and on the expression of a transcript corresponding to a neuron derived neurotrophic factor (NENF) in four cell lines of different origin, Jurkat, TK6, HeLa, and HFL1. 27 All the analyzed genes were modulated by IR but in different manners, depending o the type of cell line, thus indicating a cell type specific involvement of different pathway in response to IR treatment.…”

“…49 In recent years, microarray technology has been increasingly used in the field of cancer research, and analyses of gene expression have been conducted on irradiated cells from cancer and normal tissue, or on lymphocytes (either stimulated or EBV-immortalized) in order to understand the side effects of IR toxicity. 5,19,[21][22][23][24][25][26][27][28] The majority of the studies used RNA from biopsies in an attempt to identify prognostic classifiers. 50 Many analyses have been conducted on normal tissues to understand their constitutive response to IR and possibly to identify distinctive genes for sensitive individuals that could be used as biomarkers for predicting radiosensitivity ( Table 1).…”

“…20 Other studies tested the possibility that, in sensitive patients, constitutive alterations in the expression levels of specific RNAs could be associated with IR toxicity, and identified genes with different expression both in the normal injured tissue and in peripheral blood. 5,19,[21][22][23][24][25][26][27][28] By assessing these genes at baseline, i.e. before the start of therapy, it could be possible to use them as biomarkers for predicting or monitoring normal tissue toxicity of radiation therapy, 29 and thus select cases that can be directed towards a specific therapy, or change radiotherapy dosefractionation prescription or plan dose distributions.…”