Total body irradiation induced mouse small intestine senescence as a late effect

Abstract

Radiation can induce senescence in many organs and tissues; however, it is still unclear how radiation stimulates senescence in mouse small intestine. In this study, we use the bone marrow transplantation mouse model to explore the late effects of total body irradiation on small intestine. Our results showed that almost all of the body hairs of the irradiated mice were white (which is an indication of aging) 10 months after the exposure to radiation. Furthermore, compared with the age-matched control mice, there were more SA-β-galactosidase (SA-β-gal)–positive cells and an upregulation of p16 and p21 in 8 Gy–irradiated mice intestinal crypts, indicating that radiation induced senescence in the small intestine. Intestinal bacterial flora profile analysis showed that the diversity of the intestinal bacterial flora decreased in irradiated mice; in addition it showed that the principal components of the irradiated and control mice differed: there was increased abundance of Bacteroidia and a decreased abundance of Clostridia in irradiated mice. To explore the underlying mechanism, an RNA-sequence was executed; the results suggested that pancreatic secretion, and the digestion and absorption of proteins, carbohydrates, fats and vitamins were damaged in irradiated mice, which may be responsible for the body weight loss observed in irradiated mice. In summary, our study suggested that total body irradiation may induce senescence in the small intestine and damage the health status of the irradiated mice.

Acute Radiation Syndrome and the Microbiome: Impact and Review

“…As mentioned earlier, many bacterial species and microbiota changes in the skin (Plichta et al, 2017), vagina (Brotman et al, 2014;Bai et al, 2019), oral cavity (Vanhoecke et al, 2015;Zhu et al, 2017;Hou et al, 2018;Anjali et al, 2020;Nishii et al, 2020;Vesty et al, 2020), and GI of humans (Lam et al, 2012; are associated with disease severity and may even be predictive of pathogenesis. Along with the finding that some radiation-induced microbiota changes are persistent out to 6 months (Lam et al, 2012;Zhao et al, 2019;Anjali et al, 2020;Nishii et al, 2020), these data support the use of the microbiota as potentially stable biomarkers for radiation exposure and injury.…”

“…However, it has been found that severe postirradiation enteropathy is associated with low mucosal bacterial diversity ( Ferreira et al, 2019 ). In rodent studies, specific findings of microbiota changes in postirradiation fecal samples include increased abundance of the phylum Proteobacteria and family Lactobacillaceae and decreased abundance of families Lachnospiraceae , Ruminococcaceae , and Clostridiaceae , with some changes observed out to 10 months ( Lam et al, 2012 ; Goudarzi et al, 2016 ; Zhao et al, 2019 ; Li et al, 2020 ). In humans, one prospective study of nine gynecologic cancer patients found that Firmicutes and Fusobacterium phyla were significantly decreased in fecal samples pre- versus post-pelvic irradiation ( Nam et al, 2013 ).…”

P16INK4a Deletion Ameliorates Damage of Intestinal Epithelial Barrier and Microbial Dysbiosis in a Stress-Induced Premature Senescence Model of Bmi-1 Deficiency

“…After extraction, DNA was treated with DNase-free RNase to remove contaminating RNA. DNA concentration and quality were assessed ( Pandit et al, 2018 ; Zhao et al, 2019 ). Then, the DNA was stored at −20°C for use.…”

Identification and Integrated Analysis of circRNA and miRNA of Radiation-Induced Lung Injury in a Mouse Model

“…Understanding the molecular mechanism by revealing circRNA–miRNA–mRNA competitive regulatory networks is of great importance. As the recent improvement of RNA-sequencing (RNA-seq) facilitated obtaining huge and accurate results, 8 this technique has become a proper method to detect irradiation-responsive circRNAs in RILI. In a previous study, the lncRNA–miRNA–mRNA network was found to contribute to the RILI process by RNA-seq.…”