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Life Sci Space Res (Amst). 2016 Jun;9:19-47. doi: 10.1016/j.lssr.2016.05.004. Epub 2016 May 21.

Evaluating biomarkers to model cancer risk post cosmic ray exposure.

Author information

1
Lawrence Berkeley National Laboratory, Berkeley, CA, United States.
2
UT Southwestern Medical Center, Dallas, TX, United States.
3
Langley Research Center, Langley Research Center (LaRC), VA, United States.
4
Emory University, Atlanta, GA, United States.
5
CCSB-Tufts School of Medicine, Boston, MA, United States.
6
Wyle Science, Technology & Engineering Group, Houston, TX, United States.
7
Houston Methodist Research Institute, Houston, TX, United States.
8
Exogen Biotechnology, Inc., Berkeley, CA, United States.
9
Lawrence Berkeley National Laboratory, Berkeley, CA, United States. Electronic address: jmpluth@lbl.gov.

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.

KEYWORDS:

Biomarkers; Cancer risk; HZE; Modeling; Space radiation

PMID:
27345199
PMCID:
PMC5613937
DOI:
10.1016/j.lssr.2016.05.004
[Indexed for MEDLINE]
Free PMC Article

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