| First Author | Suman S | Year | 2022 |
| Journal | PLoS One | Volume | 17 |
| Issue | 12 | Pages | e0279771 |
| PubMed ID | 36584137 | Mgi Jnum | J:332268 |
| Mgi Id | MGI:7413573 | Doi | 10.1371/journal.pone.0279771 |
| Citation | Suman S, et al. (2022) Heavy-ion radiation-induced colitis and colorectal carcinogenesis in Il10-/- mice display co-activation of beta-catenin and NF-kappaB signaling. PLoS One 17(12):e0279771 |
| abstractText | Space radiation-induced gastrointestinal (GI) cancer risk models for future interplanetary astronauts are being developed that primarily rely on quantitative animal model studies to assess radiation-quality effects of heavy-ion space radiation exposure in relation to gamma-rays. While current GI-cancer risk estimation efforts are focused on sporadic GI-cancer mouse models, emerging in-vivo data on heavy-ion radiation-induced long-term GI-inflammation are indicative of a higher but undetermined risk of GI-inflammation associated cancers, such as colitis-associated cancer (CAC). Therefore, we aimed to assess radiation quality effects on colonic inflammation, colon cancer incidence, and associated signaling events using an in-vivo CAC model i.e., Il10-/- mice. Male Il10-/- mice (8-10 weeks, n = 12/group) were irradiated with either sham, gamma-rays or heavy-ions (28Si or 56Fe), and histopathological assessments for colitis and CAC were conducted at 2.5 months post-exposure. qPCR analysis for inflammation associated gene transcripts (Ptges and Tgfb1), and in-situ staining for markers of cell-proliferation (phospho-histone H3), oncogenesis (active-beta-catenin, and cyclin D1), and inflammation (phospho-p65NF-kappaB, iNOS, and COX2) were performed. Significantly higher colitis and CAC frequency were noted after heavy-ion exposure, relative to gamma and control mice. Higher CAC incidence after heavy-ion exposure was associated with greater activation of beta-catenin and NF-kappaB signaling marked by induced expression of common downstream inflammatory (iNOS and COX2) and pro-proliferative (Cyclin D1) targets. In summary, IR-induced colitis and CAC incidence in Il10-/- mice depends on radiation quality and display co-activation of beta-catenin and NF-kappaB signaling. |
