Dose Dependence and Sequential Changes in Mouse Small Intestinal Weight Induced by Ionizing Radiation.

Glucagon-like peptide 2 (GLP-2) has recently been identified as a novel intestinal growth factor. Because experimental diabetes is associated with bowel growth, we examined the relationship between GLP-2 and intestinal growth in rats made diabetic by streptozotocin (STZ) injection and treated with or without insulin for 3 wk. Ileal concentrations of the intestinal proglucagon-derived peptides, i.e., glicentin + oxyntomodulin, and GLPs 1 and 2, were increased by 57 ± 20% above those of controls in untreated STZ diabetes ( P < 0.05–0.001). Similar increases in plasma concentrations of glicentin + oxyntomodulin (77 ± 15% above controls, P < 0.01) and GLP-2 (91 ± 32% above controls, P < 0.05) were seen in untreated STZ diabetes. Both wet and dry small intestinal weight increased by 74 ± 20% above controls ( P < 0.01) in STZ diabetes, and macromolecular analysis indicated parallel increases in both protein ( P < 0.001) and lipid ( P < 0.05) content. Villus height ( P < 0.001) and crypt depth ( P < 0.01) were also increased in untreated diabetic rat intestine. Insulin therapy prevented the changes in plasma GLP-2 and intestinal mass seen in untreated STZ diabetes. Thus STZ diabetes is associated with both increased production of GLP-2 and enhanced bowel weight, thereby suggesting a role for GLP-2 in diabetes-associated bowel growth.

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Dose dependence effects of ionizing radiation on bile acid metabolism in the rat

International Journal of Radiation Biology ◽

10.1080/09553000110087362 ◽

2002 ◽

Vol 78 (1) ◽

pp. 41-47 ◽

Cited By ~ 3

Author(s):

P. Scanff ◽

S. Grison ◽

T. Marais ◽

P. Gourmelon ◽

N. M. Griffiths

Keyword(s):

Bile Acid ◽

Ionizing Radiation ◽

Acid Metabolism ◽

Dose Dependence ◽

Bile Acid Metabolism

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Analyzing the dose-dependence of the Saccharomyces cerevisiae global transcriptional response to methyl methanesulfonate and ionizing radiation

BMC Genomics ◽

10.1186/1471-2164-7-305 ◽

2006 ◽

Vol 7 (1) ◽

Cited By ~ 26

Author(s):

Michael G Benton ◽

Swetha Somasundaram ◽

Jeremy D Glasner ◽

Sean P Palecek

Keyword(s):

Saccharomyces Cerevisiae ◽

Ionizing Radiation ◽

Transcriptional Response ◽

Dose Dependence ◽

Methyl Methanesulfonate

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The effect of trypsin inhibitor on the pancreas and small intestine of mice

British Journal Of Nutrition ◽

10.1079/bjn19930126 ◽

1993 ◽

Vol 70 (1) ◽

pp. 333-345 ◽

Cited By ~ 19

Author(s):

Y. C. Ge ◽

R. G. H. Morgan

Keyword(s):

Small Intestine ◽

Trypsin Inhibitor ◽

Growth Rates ◽

Intestinal Growth ◽

Pancreatic Growth ◽

Bovine Trypsin ◽

Bean Flour ◽

Mucosal Layer ◽

Small Intestinal ◽

Intestinal Weight

Pancreatic and intestinal growth rates were measured in mice fed on raw soya-bean flour (RSF) for up to 24 weeks. Control animals were fed on standard chow. The effects of RSF on the mouse pancreas resembled that seen in rats, showing hypertrophy with some hyperplasia. A marked increase in small intestinal weight was also found in mice fed on RSF but not in rats fed on this diet. Histological studies showed an increase in both villous and crypt thicknesses in the small intestine from these mice, and DNA, RNA and protein measurements indicated that the increase in intestinal weight was due to hypertrophy and hyperplasia of the mucosal layer. To determine whether the intestinal growth in mice fed on RSF was purely a response to the trypsin inhibitor (TI) component of the diet, pancreatic and intestinal growth rates were also determined in mice fed on the synthetic trypsin inhibitor camostate, at levels of 0·5 or 2 g/kg in rat chow, for periods of 1–8 weeks. Control animals were fed on standard chow. RSF and 0·5 g camostate/kg had similar trypsin inhibitor activities (measured against bovine trypsin), and both caused similar increases in pancreatic weight, DNA, RNA and protein content. However, 0·5 g camostate/kg did not affect small intestinal weight. Chow containing 2 g camostate/kg contained twice as much TI activity as the RSF diet but produced only a small increase in small intestinal weight at 2 and 8 weeks. This intestinal growth was significantly less than that seen with RSF. The present study shows that, in the mouse, RSF or a diet containing camostate in the appropriate dose produces pancreatic growth comparable to that seen in the rat. RSF also causes intestinal growth, but camostate-containing diets have little or no effect on the growth of the intestine.

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Effects of fractionated doses of ionizing radiation on small intestinal motor activity

Gastroenterology ◽

10.1016/0016-5085(88)90358-7 ◽

1988 ◽

Vol 95 (5) ◽

pp. 1249-1257 ◽

Cited By ~ 53

Author(s):

Mary F. Otterson ◽

Sushil K. Sarna ◽

John E. Moulder

Keyword(s):

Ionizing Radiation ◽

Motor Activity ◽

Small Intestinal

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Quantification of radiation-induced DNA double strand break repair foci to evaluate and predict biological responses to ionizing radiation

NAR Cancer ◽

10.1093/narcan/zcab046 ◽

2021 ◽

Vol 3 (4) ◽

Author(s):

Sébastien Penninckx ◽

Eloise Pariset ◽

Egle Cekanaviciute ◽

Sylvain V Costes

Keyword(s):

Ionizing Radiation ◽

Time Course ◽

Dose Dependence ◽

Strand Break ◽

Double Strand Break ◽

Confounding Factors ◽

Dna Double Strand Break ◽

Biological Interpretation ◽

Radiation Induced

Abstract Radiation-induced foci (RIF) are nuclear puncta visualized by immunostaining of proteins that regulate DNA double-strand break (DSB) repair after exposure to ionizing radiation. RIF are a standard metric for measuring DSB formation and repair in clinical, environmental and space radiobiology. The time course and dose dependence of their formation has great potential to predict in vivo responses to ionizing radiation, predisposition to cancer and probability of adverse reactions to radiotherapy. However, increasing complexity of experimentally and therapeutically setups (charged particle, FLASH …) is associated with several confounding factors that must be taken into account when interpreting RIF values. In this review, we discuss the spatiotemporal characteristics of RIF development after irradiation, addressing the common confounding factors, including cell proliferation and foci merging. We also describe the relevant endpoints and mathematical models that enable accurate biological interpretation of RIF formation and resolution. Finally, we discuss the use of RIF as a biomarker for quantification and prediction of in vivo radiation responses, including important caveats relating to the choice of the biological endpoint and the detection method. This review intends to help scientific community design radiobiology experiments using RIF as a key metric and to provide suggestions for their biological interpretation.

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Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice

Journal of Radiation Research ◽

10.1093/jrr/rrt077 ◽

2013 ◽

Vol 54 (6) ◽

pp. 1057-1064 ◽

Cited By ~ 5

Author(s):

Hiroshi Ishihara ◽

Izumi Tanaka ◽

Haruko Yakumaru ◽

Mika Tanaka ◽

Kazuko Yokochi ◽

...

Keyword(s):

Ionizing Radiation ◽

Intestinal Mucosa ◽

Small Intestinal Mucosa ◽

Pharmaceutical Drugs ◽

Small Intestinal

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Carcinogenic Effects of Exogenous and Endogenous Glucagon-Like Peptide-2 in Azoxymethane-Treated Mice

Endocrinology ◽

10.1210/en.2009-0295 ◽

2009 ◽

Vol 150 (9) ◽

pp. 4033-4043 ◽

Cited By ~ 40

Author(s):

Roman Iakoubov ◽

Lina M. Lauffer ◽

Shivangi Trivedi ◽

Young-In J. Kim ◽

Patricia L. Brubaker

Keyword(s):

Body Weight ◽

Colon Carcinogenesis ◽

Aberrant Crypt Foci ◽

Carcinogenic Effects ◽

Human Therapy ◽

Intestinal Proliferation ◽

Glucagon Like Peptide ◽

Small Intestinal ◽

Long Acting ◽

Intestinal Weight

Abstract Glucagon-like peptide-2 (GLP-2) is a nutrient-dependent intestinotropic hormone that promotes intestinal growth, via increased intestinal proliferation and decreased apoptosis, as well as increases in nutrient absorption and barrier function. The long-acting analog h(Gly2)GLP-2[1-33] is currently being tested for treatment of short bowel syndrome and Crohn’s disease. However, the role of GLP-2 in colon carcinogenesis is controversial. To assess the intestinotropic effects of exogenous and endogenous GLP-2, C57BL6/J mice were injected with 1μg h(Gly2)GLP-2[1-33]; 30 or 60 ng hGLP-2[3-33], a GLP-2 receptor antagonist; or PBS (4 wk, twice a day, sc). Chronic h(Gly2)GLP-2[1-33] increased small intestinal weight/body weight (P < 0.001), villus height (P < 0.001), crypt depth (P < 0.001), and crypt cell proliferation, as measured by expression of the proliferative marker Ki67 (P < 0.05–0.01). In contrast, chronic hGLP-2[3-33] decreased small intestinal weight/body weight (P < 0.05) and colon weight/body weight (P < 0.05). To assess the carcinogenic effects of endogenous and exogenous GLP-2, separate mice were injected with azoxymethane (10 mg/kg, 4 wk, every 7 d, ip), followed by 1.5 μg h(Gly2)GLP-2[1-33], 30 ng hGLP-2[3-33], or PBS (4 wk, twice a day, sc) 2 or 12 wk thereafter. At 10 or 46 wk after azoxymethane treatment, the numbers of aberrant crypt foci increased with h(Gly2)GLP-2[1-33] (P < 0.001) and decreased with hGLP-2[3-33] (P < 0.01–0.05) treatment. Furthermore, mucin-depleted aberrant foci, consistent with progressive dysplasia, were almost exclusively present in h(Gly2)GLP-2[1-33]-treated mice (P < 0.01–0.001). Additionally, adenocarcinomas developed in h(Gly2)GLP-2[1-33]-treated mice but not in those receiving hGLP-2[3-33] or PBS. Taken together, these studies indicate that chronic treatment with GLP-2 enhances colon carcinogenesis, whereas antagonism of the GLP-2 receptor decreases dysplasia, with possible implications for human therapy.

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