Understanding cancer development processes after HZE-particle exposure: roles of ROS, DNA damage repair and inflammation

D. M. Sridharan, A. Asaithamby, S. M. Bailey, S. V. Costes, P. W. Doetsch, W. S. Dynan, A. Kronenberg, K. N. Rithidech, J. Saha, A. M. Snijders, E. Werner, C. Wiese, F. A. Cucinotta, J. M. Pluth

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

During space travel astronauts are exposed to a variety of radiations, including galactic cosmic rays composed of high-energy protons and high-energy charged (HZE) nuclei, and solar particle events containing low- to medium-energy protons. Risks from these exposures include carcinogenesis, central nervous system damage and degenerative tissue effects. Currently, career radiation limits are based on estimates of fatal cancer risks calculated using a model that incorporates human epidemiological data from exposed populations, estimates of relative biological effectiveness and dose-response data from relevant mammalian experimental models. A major goal of space radiation risk assessment is to link mechanistic data from biological studies at NASA Space Radiation Laboratory and other particle accelerators with risk models. Early phenotypes of HZE exposure, such as the induction of reactive oxygen species, DNA damage signaling and inflammation, are sensitive to HZE damage complexity. This review summarizes our current understanding of critical areas within the DNA damage and oxidative stress arena and provides insight into their mechanistic interdependence and their usefulness in accurately modeling cancer and other risks in astronauts exposed to space radiation. Our ultimate goals are to examine potential links and crosstalk between early response modules activated by charged particle exposure, to identify critical areas that require further research and to use these data to reduced uncertainties in modeling cancer risk for astronauts. A clearer understanding of the links between early mechanistic aspects of high-LET response and later surrogate cancer end points could reveal key nodes that can be therapeutically targeted to mitigate the health effects from charged particle exposures.

Original languageEnglish (US)
Pages (from-to)1-26
Number of pages26
JournalRadiation Research
Volume183
Issue number1
DOIs
StatePublished - Jan 1 2015

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Cosmic Radiation
DNA Repair
DNA Damage
Astronauts
deoxyribonucleic acid
cancer
extraterrestrial radiation
astronauts
Radiation
Inflammation
damage
Neoplasms
proton energy
Protons
charged particles
Solar Activity
Relative Biological Effectiveness
United States National Aeronautics and Space Administration
Linear Energy Transfer
data links

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Understanding cancer development processes after HZE-particle exposure : roles of ROS, DNA damage repair and inflammation. / Sridharan, D. M.; Asaithamby, A.; Bailey, S. M.; Costes, S. V.; Doetsch, P. W.; Dynan, W. S.; Kronenberg, A.; Rithidech, K. N.; Saha, J.; Snijders, A. M.; Werner, E.; Wiese, C.; Cucinotta, F. A.; Pluth, J. M.

In: Radiation Research, Vol. 183, No. 1, 01.01.2015, p. 1-26.

Research output: Contribution to journalArticle

Sridharan, DM, Asaithamby, A, Bailey, SM, Costes, SV, Doetsch, PW, Dynan, WS, Kronenberg, A, Rithidech, KN, Saha, J, Snijders, AM, Werner, E, Wiese, C, Cucinotta, FA & Pluth, JM 2015, 'Understanding cancer development processes after HZE-particle exposure: roles of ROS, DNA damage repair and inflammation', Radiation Research, vol. 183, no. 1, pp. 1-26. https://doi.org/10.1667/RR13804.1
Sridharan, D. M. ; Asaithamby, A. ; Bailey, S. M. ; Costes, S. V. ; Doetsch, P. W. ; Dynan, W. S. ; Kronenberg, A. ; Rithidech, K. N. ; Saha, J. ; Snijders, A. M. ; Werner, E. ; Wiese, C. ; Cucinotta, F. A. ; Pluth, J. M. / Understanding cancer development processes after HZE-particle exposure : roles of ROS, DNA damage repair and inflammation. In: Radiation Research. 2015 ; Vol. 183, No. 1. pp. 1-26.
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