Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects

Shuryak, Igor; Sachs, Rainer K.; Brenner, David J.

doi:10.1038/s41598-021-02883-y

Quantitative modeling of carcinogenesis induced by single beams or mixtures of space radiations using targeted and non-targeted effects

Journal Article · Sun Dec 05 23:00:00 EST 2021 · Scientific Reports

DOI:https://doi.org/10.1038/s41598-021-02883-y· OSTI ID:1834213

Shuryak, Igor; Sachs, Rainer K.; Brenner, David J.

Abstract

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 γ 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 γ 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.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 1834213

Journal Information:: Scientific Reports, Journal Name: Scientific Reports Journal Issue: 1 Vol. 11; ISSN 2045-2322

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United Kingdom

Language:: English

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