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Title: Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: Wemore » observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.« less
Authors:
 [1] ;  [2] ;  [3] ;  [1] ;  [2] ; ;  [4] ;  [1] ;  [2] ;  [1] ;  [2] ;  [5]
  1. Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States)
  2. (United States)
  3. (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands)
  4. Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States)
  5. (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)
Publication Date:
OSTI Identifier:
22149737
Resource Type:
Journal Article
Resource Relation:
Journal Name: International Journal of Radiation Oncology, Biology and Physics; Journal Volume: 85; Journal Issue: 1; Other Information: Copyright (c) 2013 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
62 RADIOLOGY AND NUCLEAR MEDICINE; ADENOMAS; ESTROGENS; FEMALES; IN VIVO; LARGE INTESTINE; MALES; MICE; MUCOUS MEMBRANES; MUTANTS; RADIATION DOSES; RECEPTORS; SEX; SEX DEPENDENCE