Evaluating biomarkers to model cancer risk post cosmic ray exposure
Year: 2016
Type: review
Abstract: Robust predictive models are essential to manage the risk of radiation-induced carcinogenesis. Chronic exposure to cosmic rays in the context of the complex deep space environment may place astronauts at high cancer risk. To estimate this risk, it is critical to understand how radiation-induced cellular stress impacts cell fate decisions and how this in turn alters the risk of carcinogenesis. Exposure to the heavy ion component of cosmic rays triggers a multitude of cellular changes, depending on the rate of exposure, the type of damage incurred and individual susceptibility. Heterogeneity in dose, dose rate, radiation quality, energy and particle flux contribute to the complexity of risk assessment. To unravel the impact of each of these factors, it is critical to identify sensitive biomarkers that can serve as inputs for robust modeling of individual risk of cancer or other long-term health consequences of exposure. Limitations in sensitivity of biomarkers to dose and dose rate, and the complexity of longitudinal monitoring, are some of the factors that increase uncertainties in the output from risk prediction models. Here, we critically evaluate candidate early and late biomarkers of radiation exposure and discuss their usefulness in predicting cell fate decisions. Some of the biomarkers we have reviewed include complex clustered DNA damage, persistent DNA repair foci, reactive oxygen species, chromosome aberrations and inflammation. Other biomarkers discussed, often assayed for at longer points post exposure, include mutations, chromosome aberrations, reactive oxygen species and telomere length changes. We discuss the relationship of biomarkers to different potential cell fates, including proliferation, apoptosis, senescence, and loss of stemness, which can propagate genomic instability and alter tissue composition and the underlying mRNA signatures that contribute to cell fate decisions. Our goal is to highlight factors that are important in choosing biomarkers and to evaluate the potential for biomarkers to inform models of post exposure cancer risk. Because cellular stress response pathways to space radiation and environmental carcinogens share common nodes, biomarker-driven risk models may be broadly applicable for estimating risks for other carcinogens.
Source: Life Sciences in Space Research
Authors: Deepa M. Sridharan, Aroumougame Asaithamby, Steve R. Blattnig, Sylvain V. Costes, Paul W. Doetsch, William S. Dynan, Philip Hahnfeldt, Lynn Hlatky, Yared Kidane, Amy Kronenberg, Mamta D. Naidu, Leif E. Peterson, Ianik Plante, Artem L. Ponomarev, Janapriya Saha, Antoine M. Snijders, Kalayarasan Srinivasan, Jonathan Tang, Erica Werner, Janice M. Pluth
Language: English
Subfield: Radiology, Nuclear Medicine and Imaging
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,060
Awards: G1308689833, Laser Capture Microscopy and 2D-DIGE: Cancer Proteomics, EXOSOMES AND SECRETORY FACTORS AS MEDIATORS OF NON-TARGETED EFFECTS OF HZE PARTICLES. THIS IS A PROPOSAL DEVOTED TO UNDERSTANDING THE MECHANISM OF RA, WE PROPOSE TO STUDY THE IR-INDUCED DNA DAMAGE REPAIR MECHANISM(S), WITH A PRIMARY FOCUS ON BER, THE PREDOMINANT PATHWAY UP-REGULATED IN MITOCHONDRIA., G3933523533, NASALS RADIATION RESEARCH PROGRAM IS FOCUSED ON ASSURING THAT HUMANS CAN TRAVEL IN SPACE WITHOUT EXCEEDING THE LIMITING RISKS FROM RADIATION, AND ON, G42916606, G4846573338, THE GOAL OF OUR INVESTIGATION IS TO PROVIDE MULTI-SCALE DATA FOR AN IMPROVED MECHANISTIC UNDERSTANDING, AND AN AUGMENTED CONCEPTUAL FRAMEWORK FOR NAS, G63929062, DNA DAMAGE AND CONSEQUENT MUTATIONS INITIATE THE MULTI-STEP CARCINOGENIC PROCESS. SUBSTANTIAL EVIDENCE INDICATES THAT HIGH CHARGE AND ENERGY [HZE] PA, G6832679904, THE BASIC PREMISE DRIVING OUR NSCOR EFFORT IS THAT INTERCELLULAR INTERACTIONS, AS MODIFIED BY SPACE RADIATIONS, CAN PLAY AN IMPORTANT, OFTEN DECISIVE, THE PURPOSE OF THE COMPUTATION CORE TASK IS TO PROVIDE COMPUTATIONAL AND ALGORITHM DEVELOPMENT SUPPORT FOR DATA FUSION AND INTEGRATION OF EXISTING CE, G7895028338, THE RISKS TO ASTRONAUTS FROM EXPOSURE TO SPACE RADIATION HAVE LONG BEEN OF GREAT CONCERN TO NASA. THESE RISKS ARE NOW MORE IMPORTANT WITH THE ADVENT
OpenAlex ID: W2396533964