PMID- 34873209
OWN - NLM
STAT- MEDLINE
DCOM- 20220124
LR  - 20220124
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Dec 6
TI  - Quantitative modeling of carcinogenesis induced by single beams or mixtures of 
      space radiations using targeted and non-targeted effects.
PG  - 23467
LID - 10.1038/s41598-021-02883-y [doi]
LID - 23467
AB  - Ionizing radiations encountered by astronauts on deep space missions produce 
      biological damage by two main mechanisms: (1) Targeted effects (TE) due to direct 
      traversals of cells by ionizing tracks. (2) Non-targeted effects (NTE) caused by 
      release of signals from directly hit cells. The combination of these mechanisms 
      generates non-linear dose response shapes, which need to be modeled 
      quantitatively to predict health risks from space exploration. Here we used a 
      TE + NTE model to analyze data on APC((1638N/+)) mouse tumorigenesis induced by 
      space-relevant doses of protons, (4)He, (12)C, (16)O, (28)Si or (56)Fe ions, or gamma 
      rays. A customized weighted Negative Binomial distribution was used to describe 
      the radiation type- and dose-dependent data variability. This approach allowed 
      detailed quantification of dose-response shapes, NTE- and TE-related model 
      parameters, and radiation quality metrics (relative biological effectiveness, 
      RBE, and radiation effects ratio, RER, relative to gamma rays) for each radiation 
      type. Based on the modeled responses for each radiation type, we predicted the 
      tumor yield for a Mars-mission-relevant mixture of these radiations, using the 
      recently-developed incremental effect additivity (IEA) synergy theory. The 
      proposed modeling approach can enhance current knowledge about quantification of 
      space radiation quality effects, dose response shapes, and ultimately the health 
      risks for astronauts.
CI  - (c) 2021. The Author(s).
FAU - Shuryak, Igor
AU  - Shuryak I
AD  - Center for Radiological Research, Columbia University Irving Medical Center, 630 
      West 168th St., New York, NY, 10032, USA. is144@cumc.columbia.edu.
FAU - Sachs, Rainer K
AU  - Sachs RK
AD  - Department of Mathematics, University of California, Berkeley, CA, 94720, USA.
FAU - Brenner, David J
AU  - Brenner DJ
AD  - Center for Radiological Research, Columbia University Irving Medical Center, 630 
      West 168th St., New York, NY, 10032, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20211206
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Protons)
SB  - IM
MH  - Animals
MH  - Carcinogenesis/*radiation effects
MH  - Cell Transformation, Neoplastic/*radiation effects
MH  - Cosmic Radiation/*adverse effects
MH  - Gamma Rays/adverse effects
MH  - Humans
MH  - Linear Energy Transfer/radiation effects
MH  - Male
MH  - Mice
MH  - Neoplasms, Radiation-Induced/etiology
MH  - Protons/adverse effects
MH  - Relative Biological Effectiveness
MH  - Space Flight
PMC - PMC8648899
COIS- The authors declare no competing interests.
EDAT- 2021/12/08 06:00
MHDA- 2022/01/27 06:00
PMCR- 2021/12/06
CRDT- 2021/12/07 06:16
PHST- 2021/09/03 00:00 [received]
PHST- 2021/11/24 00:00 [accepted]
PHST- 2021/12/07 06:16 [entrez]
PHST- 2021/12/08 06:00 [pubmed]
PHST- 2022/01/27 06:00 [medline]
PHST- 2021/12/06 00:00 [pmc-release]
AID - 10.1038/s41598-021-02883-y [pii]
AID - 2883 [pii]
AID - 10.1038/s41598-021-02883-y [doi]
PST - epublish
SO  - Sci Rep. 2021 Dec 6;11(1):23467. doi: 10.1038/s41598-021-02883-y.