Elevated SASP Factors, Reduced Antioxidant Enzymes, and Increased Tumor Susceptibility in Space Radiation-Exposed ApcMin/+ Mice

Q: What radiation model and subject are used to study cancer risk?

Female ApcMin/+ mice are exposed to 75 cGy simulated galactic cosmic radiation, and serum and tissue samples are collected 100–110 days post-exposure for molecular and histopathological analyses.

Q: How did the study assess whether tumor susceptibility increased?

Tumor incidence is scored by blinded observers, and molecular changes are evaluated using TMT-based proteomics alongside validation by immunoblotting, ELISA, and enzyme activity assays.

Q: Which serum biomarker-related changes were highlighted after GCR exposure?

GCR exposure increases GI and mammary tumor burden and produces a proteomic signature with elevated TGF-β1 and MMP9, while key antioxidant defenses show reduced levels and enzymatic activities; cross-referencing identifies 11 SASP-associated proteins linked to human cancers.

Sep 30, 2026

Uploaded by Genevieve

Human missions into deep space will expose astronauts to galactic cosmic radiation (GCR), a mixed high-energy particle field predicted to raise long-term cancer risk. To enable biomarker-based risk stratification and mitigation, this work uses Tandem Mass Tag (TMT) quantitative proteomics in female ApcMin/+ mice exposed to 75 cGy simulated GCR. Molecular and histopathology analyses at 100–110 days show increased GI and mammary tumor burden. Proteomics identifies 194 upregulated and 461 downregulated serum proteins with pathway shifts and reduced antioxidant defenses, including elevated TGF-β1 and MMP9. Cross-referencing 36 GCR-induced SASP factors links 11 proteins to human breast and colorectal cancers, suggesting a pro-tumorigenic serum signature for astronaut risk assessment.

LanguageEnglish

CategoryHealthcare

FormatPDF

Pages23

Reading Time58 min

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Abstract

1. Introduction

Article Elevated SASP Factors, Reduced Antioxidant Enzymes, and Increased Tumor Susceptibility in Space Radiation-Exposed ApcMin/+ Mice Kamendra Kumar 1, Jerry Angdisen 1, Albert J. Fornace, Jr. 1,2 and Shubhankar Suman 1, * Academic Editor: ErikA.C. Wiemer Received: 20 November 2025 Revised: 16 December 2025 Accepted: 19 December 2025 Published: 24 December 2025 Copyright: © 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license. 1 Department of Oncology, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, DC 20057, USA; [kk1264@georgetown.edu](kk1264@georgetown.edu) (K.K.); [jja87@georgetown.edu](jja87@georgetown.edu) (J.A.) 2 Department of Biochemistry and Molecular & Cellular Biology, Georgetown University Medical Center, Washington, DC 20057, USA * Correspondence: [ss2286@georgetown.edu](ss2286@georgetown.edu); Tel.: +1-202-687-3104 Abstract Human missions into deep space will expose astronauts to the unique and complex radiation environment of galactic cosmic radiation (GCR), a mixed field of high-energy protons and heavy ions predicted to substantially increase long-term cancer risk. To support effective risk stratification, early detection, and mitigation strategies, there is a need to identify biomarkers indicative of GCR-induced cancer risk. Here, we applied a Tandem Mass Tag (TMT)-based quantitative proteomics approach to identify potential biomarkers associated with GCR-induced gastrointestinal (GI) and mammary tumorigenesis using the female ApcMin/+ mouse, a well-established model of human colorectal and breast cancer. Eight-to ten-week-old ApcMin/+ mice were exposed to 75 cGy of simulated GCR and serum and tissue samples were collected 100–110 days post-exposure for molecular and histopathological analyses. Tumor incidence was scored by blinded observers, and serum proteomes exhibiting a fold change > 1.2 or <0.83 with p < 0.05 were considered significantly altered. Bioinformatics analyses, including Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway enrichment, and unsupervised clustering, were employed to delineate GCR-responsive molecular networks. Validation of differentially expressed proteins (DEPs) was performed using immunoblotting, ELISA, and enzyme activity assays. GCR exposure resulted in a significant increase in both GI and mammary tumor burden relative to controls. Proteomic profiling revealed 194 upregulated and 461 downregulated proteins, distinguishing GCR-exposed from control serum proteomes. Functional enrichment analyses highlighted alterations in metabolic processes, PI3K-AKT, HIF-1, and PPAR signaling pathways, alongside the suppression of antioxidant defense mechanisms. Notably, mice exposed to GCR exhibited elevated serum levels of TGF-β1 and MMP9, accompanied by reduced levels and enzymatic activities of key antioxidant defenses. Cross-referencing 36 GCR-induced serum SASP factors with the Human Protein Atlas revealed 11 SASP proteins associated with human breast and colorectal cancers. Together, these findings show that GCR exposure triggers a pro-tumorigenic serum proteomic signature that may serve as a biomarker for assessing cancer risk in astronauts during deep-space missions. Keywords: space radiation; galactic cosmic radiation; cancer risk; antioxidant enzymes; senescence-associated secretory phenotype (SASP) factors; risk biomarkers 1. Introduction Manned missions beyond Earth’s magnetosphere, including future expeditions to Mars, will inevitably expose astronauts to the ionizing radiation (IR) environment of deep space [1–3] . The deep-space radiation environment is dominated by two principal components: galactic cosmic radiation (GCR) and solar particle events (SPEs) . While SPEs consist of intermittent bursts of low-to medium-energy protons emitted from the Sun, GCR

FAQs

What radiation model and subject are used to study cancer risk?

Female ApcMin/+ mice are exposed to 75 cGy simulated galactic cosmic radiation, and serum and tissue samples are collected 100–110 days post-exposure for molecular and histopathological analyses.

How did the study assess whether tumor susceptibility increased?

Tumor incidence is scored by blinded observers, and molecular changes are evaluated using TMT-based proteomics alongside validation by immunoblotting, ELISA, and enzyme activity assays.

Which serum biomarker-related changes were highlighted after GCR exposure?

GCR exposure increases GI and mammary tumor burden and produces a proteomic signature with elevated TGF-β1 and MMP9, while key antioxidant defenses show reduced levels and enzymatic activities; cross-referencing identifies 11 SASP-associated proteins linked to human cancers.

Sep 30, 2026

Uploaded by Genevieve