TY - JOUR
T1 - Evaluating biomarkers to model cancer risk post cosmic ray exposure
AU - Sridharan, Deepa M.
AU - Asaithamby, Aroumougame
AU - Blattnig, Steve R.
AU - Costes, Sylvain V.
AU - Doetsch, Paul W.
AU - Dynan, William S.
AU - Hahnfeldt, Philip
AU - Hlatky, Lynn
AU - Kidane, Yared
AU - Kronenberg, Amy
AU - Naidu, Mamta D.
AU - Peterson, Leif E.
AU - Plante, Ianik
AU - Ponomarev, Artem L.
AU - Saha, Janapriya
AU - Snijders, Antoine M.
AU - Srinivasan, Kalayarasan
AU - Tang, Jonathan
AU - Werner, Erica
AU - Pluth, Janice M.
N1 - Publisher Copyright:
© 2016 The Committee on Space Research (COSPAR)
PY - 2016
Y1 - 2016
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Cancer risk
KW - HZE
KW - Modeling
KW - Space radiation
UR - http://www.scopus.com/inward/record.url?scp=84979642676&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84979642676&partnerID=8YFLogxK
U2 - 10.1016/j.lssr.2016.05.004
DO - 10.1016/j.lssr.2016.05.004
M3 - Review article
C2 - 27345199
AN - SCOPUS:84979642676
SN - 2214-5524
VL - 9
SP - 19
EP - 47
JO - Life Sciences in Space Research
JF - Life Sciences in Space Research
ER -