Systems biology perspectives on the carcinogenic potential of radiation

Barcellos-Hoff, Mary Helen; Adams, Cassandra; Balmain, Allan; Costes, Sylvain V.; Demaria, Sandra; Illa-Bochaca, Irineu; Mao, Jian Hua; Ouyang, Haoxu; Sebastiano, Christopher; Tang, Jonathan

doi:10.1093/jrr/rrt211

Systems biology perspectives on the carcinogenic potential of radiation

Journal Article · Fri Feb 28 23:00:00 EST 2014 · Journal of Radiation Research

DOI:https://doi.org/10.1093/jrr/rrt211· OSTI ID:1625353

Barcellos-Hoff, Mary Helen ^[1]; Adams, Cassandra ^[2]; Balmain, Allan ^[2]; Costes, Sylvain V. ^[3]; Demaria, Sandra ^[4]; Illa-Bochaca, Irineu ^[5]; Mao, Jian Hua ^[3]; Ouyang, Haoxu ^[5]; Sebastiano, Christopher ^[6]; Tang, Jonathan ^[3]

New York Univ. (NYU), NY (United States). School of Medicine, Dept. of Radiation Oncology; DOE/OSTI
Univ. of California, San Francisco, CA (United States). Helen Diller Family Comprehensive Cancer Center
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Life Sciences Division
New York Univ. (NYU), NY (United States). School of Medicine, Dept. of Pathology
New York Univ. (NYU), NY (United States). School of Medicine, Dept. of Radiation Oncology
New York Univ. (NYU), NY (United States), School of Medicine. Dept. of Pathology

This review focuses on recent experimental and modeling studies that attempt to define the physiological context in which high linear energy transfer (LET) radiation increases epithelial cancer risk and the efficiency with which it does so. Radiation carcinogenesis is a two-compartment problem: ionizing radiation can alter genomic sequence as a result of damage due to targeted effects (TE) from the interaction of energy and DNA; it can also alter phenotype and multicellular interactions that contribute to cancer by poorly understood nontargeted effects (NTE). Rather than being secondary to DNA damage and mutations that can initiate cancer, radiation NTE create the critical context in which to promote cancer. Systems biology modeling using comprehensive experimental data that integrates different levels of biological organization and time-scales is a means of identifying the key processes underlying the carcinogenic potential of high-LET radiation. We hypothesize that inflammation is a key process, and thus cancer susceptibility will depend on specific genetic predisposition to the type and duration of this response. Systems genetics using novel mouse models can be used to identify such determinants of susceptibility to cancer in radiation sensitive tissues following high-LET radiation. Improved understanding of radiation carcinogenesis achieved by defining the relative contribution of NTE carcinogenic effects and identifying the genetic determinants of the high-LET cancer susceptibility will help reduce uncertainties in radiation risk assessment.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)

Sponsoring Organization:: USDOE Office of Science (SC), Biological and Environmental Research (BER). Biological Systems Science Division; National Aeronautics and Space Administration (NASA)

OSTI ID:: 1625353

Alternate ID(s):: OSTI ID: 22404402

Journal Information:: Journal of Radiation Research, Journal Name: Journal of Radiation Research Journal Issue: suppl 1 Vol. 55; ISSN 0449-3060

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

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59 BASIC BIOLOGICAL SCIENCES
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63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
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