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Cited by 11Inflammatory mediators and NSAID effectsEffects of Radiation ExposureRadiation Therapy and Dosimetry

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Effects of dietary aspirin on high-LET radiation-induced prostaglandin E2 levels and gastrointestinal tumorigenesis in Apc mice

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Suman, Shubhankar, Kumar, Santosh, Moon, Bo-Hyun, Angdisen, Jerry, Kallakury, Bhaskar V.S., Datta, Kamal, Fornace Jr, Albert J.·2021·Life Sciences in Space Research
DOI 10.1016/j.lssr.2021.09.001PMC PMC9808916
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Abstract

Inevitable exposure to high-LET ionizing radiation (IR) present in galactic cosmic radiation (GCR) could enhance gastrointestinal (GI) cancer incidence among astronauts undertaking deep space exploration and GI-cancer mortality has been predicted to far exceed NASA's limit of < 3% REID (Radiation exposure-induced death) from cancer. Therefore, the development of countermeasure agents against high-LET radiation-induced GI cancer is needed to safeguard astronauts during and after an outer space mission. The cyclooxygenase-2/prostaglandin E2 (COX2/PGE2) mediated activation of pro-inflammatory and oncogenic signaling has been reported to play an important role in persistent inflammation and GI-tumorigenesis after high-LET radiation exposure. Therefore, aspirin, a well-known inhibitor of the COX/PGE2 pathway, was evaluated as a potential countermeasure against 28 Si-induced PGE2 and tumorigenesis in Apc 1638N/+, a murine model of human GI-cancer. Animals were fed either standard or aspirin supplemented diet (75, 150, or 300 mg/day of human equivalent dose) starting at the age of 4 weeks and continued till the end of the study, while mice were exposed to 28 Si-ions (300 MeV/n; 69 keV/μm) at the age of 8 weeks. Serum PGE2 level, GI tumor size (>2mm 2), number, and cluster (>5 adjoining tumors) were analyzed at 150 days post-exposure. Aspirin led to a significant reduction in PGE2 in a dose-dependent manner but did not reduce 28 Si-induced GI tumorigenesis even at the highest (300 mg/day) dose. In summary, this study suggests that aspirin could reduce high-LET IR-induced pro-inflammatory PGE2 levels, however, lacks the ability to reduce high-LET IR-induced GI tumorigenesis in Apc 1638N/+ mice.

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Metadata

Authors
Suman, S., Kumar, S., Moon, B.-H., Angdisen, J., Kallakury, B. V. S., Datta, K., & Fornace Jr, A. J.
Affiliations
Georgetown University Medical Center (US)
Corresponding author
Suman, Shubhankar
ORCID
Venue
Life Sciences in Space Research
Publisher
Elsevier BV
Published
2021-11
Volume
31
Pages
85-91
ISSN
2214-5524 (ISSN-L)
DOI
10.1016/j.lssr.2021.09.001
PMC
PMC9808916
OpenAlex
W3201464817
Cited by
11
References
0
Citations by year
2025: 1 · 2024: 2 · 2023: 2 · 2022: 6
FWCI
1.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Life Sciences in Space Research (acceptedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Georgetown University
  • National Aeronautics and Space Administration (NNX09AU95G)
Topics
  • Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
  • Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Effects of Radiation Exposure
  • Physical Sciences › Physics and Astronomy › Radiation › Radiation Therapy and Dosimetry
Keywords
aspirin, high-LET radiation, prostaglandin E2, silicon ion irradiation, cyclooxygenase-2, radiation countermeasures, galactic cosmic rays, cyclooxygenase inhibition
MeSH terms
Animals, Aspirin, Cosmic Radiation, Diet, Dinoprostone, Mice, Carcinogenesis

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