Evaluating biomarkers to model cancer risk post cosmic ray exposure

作者：Deepa 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, Srinivasan Kalayarasan, Jonathan Tang, Erica Werner, Janice M. Pluth · 发表于：Life Sciences in Space Research · 年份：2016 · DOI：10.1016/j.lssr.2016.05.004 · 被引用次数：47 · 研究领域：Effects of Radiation Exposure、Radiation Therapy and Dosimetry、Frailty in Older Adults

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 assay...