1 research outputs found
Radiation Type- and Dose-Specific Transcriptional Responses across Healthy and Diseased Mammalian Tissues
Ionizing radiation (IR) is a genuine genotoxic agent and a major modality in cancer treatment. IR disrupts DNA sequences and exerts mutagenic and/or cytotoxic properties that not only
alter critical cellular functions but also impact tissues proximal and distal to the irradiated site.
Unveiling the molecular events governing the diverse effects of IR at the cellular and organismal
levels is relevant for both radiotherapy and radiation protection. Herein, we address changes in the
expression of mammalian genes induced after the exposure of a wide range of tissues to various
radiation types with distinct biophysical characteristics. First, we constructed a publicly available
database, termed RadBioBase, which will be updated at regular intervals. RadBioBase includes
comprehensive transcriptomes of mammalian cells across healthy and diseased tissues that respond
to a range of radiation types and doses. Pertinent information was derived from a hybrid analysis based on stringent literature mining and transcriptomic studies. An integrative bioinformatics
methodology, including functional enrichment analysis and machine learning techniques, was employed to unveil the characteristic biological pathways related to specific radiation types and their
association with various diseases. We found that the effects of high linear energy transfer (LET)
radiation on cell transcriptomes significantly differ from those caused by low LET and are consistent
with immunomodulation, inflammation, oxidative stress responses and cell death. The transcriptome
changes also depend on the dose since low doses up to 0.5 Gy are related with cytokine cascades,
while higher doses with ROS metabolism. We additionally identified distinct gene signatures for different types of radiation. Overall, our data suggest that different radiation types and doses can trigger
distinct trajectories of cell-intrinsic and cell-extrinsic pathways that hold promise to be manipulated
toward improving radiotherapy efficiency and reducing systemic radiotoxicities