Evaluating biomarkers to model cancer risk post cosmic ray exposure

• Authors: Deepa M. Sridhara, Lawrence Berkeley National Laboratory; Aroumougame Asaithamby, UT Southwestern Medical Center; Steve R. Blattnig, Langley Research Center; Sylvain V. Costes, Lawrence Berkeley National Laboratory; Paul Doetsch, Emory University; William Dynan, Emory University; Philip Hahnfeldt, Tufts University; Lynn Hlatky, Tufts University; Yared Kidane, Wyle Science; Amy Kronenberg, Lawrence Berkeley National Laboratory
• Journal Title: Life Sciences and Space Research
• Volume: Volume 9
• Publisher: Elsevier | 2016-06-01, Pages 19-47
• Type of Work: Article | Final Publisher PDF
• Publisher DOI: http://doi.org/10.1016/j.lssr.2016.05.004
• Subjects: Health Sciences, Oncology; Chemistry, Radiation
• Keywords: Biomarkers; Cancer risk; HZE; Modeling; Space radiation

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.