skip to main content
DOE PAGES title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models

Abstract

Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-set for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.

Authors:
 [1];  [1]
  1. Univ. of Nevada, Las Vegas, NV (United States)
Publication Date:
Research Org.:
Univ. of Nevada, Las Vegas, NV (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1393572
Grant/Contract Number:  
SC0012640
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 7; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.

Citation Formats

Cucinotta, Francis A., and Cacao, Eliedonna. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models. United States: N. p., 2017. Web. doi:10.1038/s41598-017-02087-3.
Cucinotta, Francis A., & Cacao, Eliedonna. Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models. United States. doi:10.1038/s41598-017-02087-3.
Cucinotta, Francis A., and Cacao, Eliedonna. Fri . "Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models". United States. doi:10.1038/s41598-017-02087-3. https://www.osti.gov/servlets/purl/1393572.
@article{osti_1393572,
title = {Non-Targeted Effects Models Predict Significantly Higher Mars Mission Cancer Risk than Targeted Effects Models},
author = {Cucinotta, Francis A. and Cacao, Eliedonna},
abstractNote = {Cancer risk is an important concern for galactic cosmic ray (GCR) exposures, which consist of a wide-energy range of protons, heavy ions and secondary radiation produced in shielding and tissues. Relative biological effectiveness (RBE) factors for surrogate cancer endpoints in cell culture models and tumor induction in mice vary considerable, including significant variations for different tissues and mouse strains. Many studies suggest non-targeted effects (NTE) occur for low doses of high linear energy transfer (LET) radiation, leading to deviation from the linear dose response model used in radiation protection. Using the mouse Harderian gland tumor experiment, the only extensive data-set for dose response modelling with a variety of particle types (>4), for the first-time a particle track structure model of tumor prevalence is used to investigate the effects of NTEs in predictions of chronic GCR exposure risk. The NTE model led to a predicted risk 2-fold higher compared to a targeted effects model. The scarcity of data with animal models for tissues that dominate human radiation cancer risk, including lung, colon, breast, liver, and stomach, suggest that studies of NTEs in other tissues are urgently needed prior to long-term space missions outside the protection of the Earth’s geomagnetic sphere.},
doi = {10.1038/s41598-017-02087-3},
journal = {Scientific Reports},
number = 1,
volume = 7,
place = {United States},
year = {2017},
month = {5}
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Citation Metrics:
Cited by: 11 works
Citation information provided by
Web of Science

Save / Share:

Works referenced in this record:

Effects of 28Si Ions, 56Fe Ions, and Protons on the Induction of Murine Acute Myeloid Leukemia and Hepatocellular Carcinoma
journal, August 2014


Incidence of Acute Myeloid Leukemia and Hepatocellular Carcinoma in Mice Irradiated with 1 GeV/nucleon 56 Fe Ions
journal, August 2009

  • Weil, Michael M.; Bedford, Joel S.; Bielefeldt-Ohmann, Helle
  • Radiation Research, Vol. 172, Issue 2
  • DOI: 10.1667/RR1648.1

Initiation-promotion model of tumor prevalence in mice from space radiation exposures
journal, August 1995

  • Cucinotta, Francis A.; Wilson, John W.
  • Radiation and Environmental Biophysics, Vol. 34, Issue 3
  • DOI: 10.1007/BF01211540

Systematic Review and Meta-analysis of Circulatory Disease from Exposure to Low-Level Ionizing Radiation and Estimates of Potential Population Mortality Risks
journal, November 2012

  • Little, Mark P.; Azizova, Tamara V.; Bazyka, Dimitry
  • Environmental Health Perspectives, Vol. 120, Issue 11
  • DOI: 10.1289/ehp.1204982

NASA Study of Cataract in Astronauts (NASCA). Report 1: Cross-Sectional Study of the Relationship of Exposure to Space Radiation and Risk of Lens Opacity
journal, July 2009

  • Chylack, Leo T.; Peterson, Leif E.; Feiveson, Alan H.
  • Radiation Research, Vol. 172, Issue 1
  • DOI: 10.1667/RR1580.1

Relative Effectiveness at 1 Gy after Acute and Fractionated Exposures of Heavy Ions with Different Linear Energy Transfer for Lung Tumorigenesis
journal, February 2015

  • Wang, Xiang; Farris III, Alton B.; Wang, Ping
  • Radiation Research, Vol. 183, Issue 2
  • DOI: 10.1667/RR13884.1

The Effects of Delta Rays on the Number of Particle-Track Traversals per Cell in Laboratory and Space Exposures
journal, July 1998

  • Cucinotta, Francis A.; Nikjoo, Hooshang; Goodhead, Dudley T.
  • Radiation Research, Vol. 150, Issue 1
  • DOI: 10.2307/3579651

Survey of Cellular Radiosensitivity Parameters
journal, December 1994

  • Katz, Robert; Zachariah, Rashidah; Cucinotta, Francis A.
  • Radiation Research, Vol. 140, Issue 3
  • DOI: 10.2307/3579113

From The Cover: Biological effects in unirradiated human tissue induced by radiation damage up to 1 mm away
journal, September 2005

  • Belyakov, O. V.; Mitchell, S. A.; Parikh, D.
  • Proceedings of the National Academy of Sciences, Vol. 102, Issue 40
  • DOI: 10.1073/pnas.0505020102

Neutron Carcinogenesis: Dose and Dose-Rate Effects in BALB/c Mice
journal, December 1977

  • Ullrich, R. L.; Jernigan, M. C.; Storer, J. B.
  • Radiation Research, Vol. 72, Issue 3
  • DOI: 10.2307/3574612

High LET constraints on low LET survival
journal, September 1978


Targeted and Nontargeted Effects of Ionizing Radiation That Impact Genomic Instability
journal, October 2008


Non-targeted effects of ionising radiation—Implications for low dose risk
journal, April 2013

  • Kadhim, Munira; Salomaa, Sisko; Wright, Eric
  • Mutation Research/Reviews in Mutation Research, Vol. 752, Issue 2
  • DOI: 10.1016/j.mrrev.2012.12.001

Measurements of Energetic Particle Radiation in Transit to Mars on the Mars Science Laboratory
journal, May 2013


HZE Radiation Non-Targeted Effects on the Microenvironment That Mediate Mammary Carcinogenesis
journal, March 2016


Comments on the DDREF Estimate of the BEIR VII Committee
journal, January 2015


Space Radiation Quality Factors and the Delta Ray Dose and Dose-Rate Reduction Effectiveness Factor
journal, January 2016


Relative Biological Effectiveness of Energetic Heavy Ions for Intestinal Tumorigenesis Shows Male Preponderance and Radiation Type and Energy Dependence in APC1638N/+ Mice
journal, May 2016

  • Suman, Shubhankar; Kumar, Santosh; Moon, Bo-Hyun
  • International Journal of Radiation Oncology*Biology*Physics, Vol. 95, Issue 1
  • DOI: 10.1016/j.ijrobp.2015.10.057

Tumor Induction in BALB/c Mice after Fractionated or Protracted Exposures to Fission-Spectrum Neutrons
journal, March 1984


No evidence for an increase in circulatory disease mortality in astronauts following space radiation exposures
journal, August 2016

  • Cucinotta, Francis A.; Hamada, Nobuyuki; Little, Mark P.
  • Life Sciences in Space Research, Vol. 10
  • DOI: 10.1016/j.lssr.2016.08.002

Role of Homologous Recombination in the Alpha-Particle-Induced Bystander Effect for Sister Chromatid Exchanges and Chromosomal Aberrations
journal, August 2005

  • Nagasawa, H.; Peng, Y.; Wilson, P. F.
  • Radiation Research, Vol. 164, Issue 2
  • DOI: 10.1667/RR3420

Issues for Simulation of Galactic Cosmic Ray Exposures for Radiobiological Research at Ground-Based Accelerators
journal, June 2015


In vivo mammary tumourigenesis in the Sprague–Dawley rat and microdosimetric correlates
journal, July 2004


Safe days in space with acceptable uncertainty from space radiation exposure
journal, April 2015


Fluence-based relative biological effectiveness for charged particle carcinogenesis in mouse Harderian gland
journal, October 1994


Propagation Distance of the α-Particle-Induced Bystander Effect: The Role of Nuclear Traversal and Gap Junction Communication
journal, May 2009

  • Gaillard, Sylvain; Pusset, David; de Toledo, Sonia M.
  • Radiation Research, Vol. 171, Issue 5
  • DOI: 10.1667/RR1658.1

Comparison of Martian surface ionizing radiation measurements from MSL-RAD with Badhwar-O'Neill 2011/HZETRN model calculations: SIMULATION OF MARTIAN SURFACE RADIATION
journal, June 2014

  • Kim, Myung-Hee Y.; Cucinotta, Francis A.; Nounu, Hatem N.
  • Journal of Geophysical Research: Planets, Vol. 119, Issue 6
  • DOI: 10.1002/2013JE004549

Induction of Chromosomal Aberrations at Fluences of Less Than One HZE Particle per Cell Nucleus
journal, October 2014

  • Hada, Megumi; Chappell, Lori J.; Wang, Minli
  • Radiation Research, Vol. 182, Issue 4
  • DOI: 10.1667/RR13721.1

Tumorigenic Potential of High-Z, High-LET Charged-Particle Radiations
journal, December 1993

  • Alpen, E. L.; Powers-Risius, P.; Curtis, S. B.
  • Radiation Research, Vol. 136, Issue 3
  • DOI: 10.2307/3578551

High-LET Radiation Carcinogenesis
journal, November 1985

  • Fry, R. J. M.; Powers-Risius, P.; Alpen, E. L.
  • Radiation Research, Vol. 104, Issue 2
  • DOI: 10.2307/3576646

The Comparative Tumorigenic Effects of Fission Neutrons and Cobalt-60 g Rays in the B6CF 1 Mouse
journal, January 1992

  • Grahn, Douglas; Lombard, Louise S.; Carnes, Bruce A.
  • Radiation Research, Vol. 129, Issue 1
  • DOI: 10.2307/3577899

Tumor Induction in BALB/c Female Mice after Fission Neutron or γ Irradiation
journal, March 1983


An initiation-promotion model of tumour prevalence from high-charge and energy radiations
journal, November 1994


Non-targeted effects and the dose response for heavy ion tumor induction
journal, May 2010

  • Cucinotta, Francis A.; Chappell, Lori J.
  • Mutation Research/Fundamental and Molecular Mechanisms of Mutagenesis, Vol. 687, Issue 1-2
  • DOI: 10.1016/j.mrfmmm.2010.01.012

Transmission of chromosomal instability after plutonium α-particle irradiation
journal, February 1992

  • Kadhim, M. A.; Macdonald, D. A.; Goodhead, D. T.
  • Nature, Vol. 355, Issue 6362
  • DOI: 10.1038/355738a0

Relative Biological Effectiveness of HZE Particles for Chromosomal Exchanges and Other Surrogate Cancer Risk Endpoints
journal, April 2016


Space radiation risks to the central nervous system
journal, July 2014


Harderian Gland Tumorigenesis: Low-Dose and LET Response
journal, May 2016

  • Chang, Polly Y.; Cucinotta, Francis A.; Bjornstad, Kathleen A.
  • Radiation Research, Vol. 185, Issue 5
  • DOI: 10.1667/RR14335.1

A New Approach to Reduce Uncertainties in Space Radiation Cancer Risk Predictions
journal, March 2015


    Works referencing / citing this record:

    Microbial cells can cooperate to resist high-level chronic ionizing radiation
    journal, December 2017


    Microbial cells can cooperate to resist high-level chronic ionizing radiation
    journal, December 2017