title: Sex-dependent differences in intestinal tumorigenesis induced in Apc1638N/+ mice by exposure to γ rays.
abstract: OBJECTIVE
  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
  Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of γ 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)-α were also assessed by immunohistochemistry.
  
  
  RESULTS
  We observed that, with both 1 Gy and 5 Gy of γ 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-α in both non tumor mucosa and intestinal tumors from irradiated male mice.
  
  
  CONCLUSIONS
  We 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.
authors.affiliation: Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia 20057, USA.
authors.forename: Daniela
authors.initials: D
authors.lastname: Trani
authors.forename: Bo-Hyun
authors.initials: BH
authors.lastname: Moon
authors.forename: Bhaskar
authors.initials: B
authors.lastname: Kallakury
authors.forename: Dan P
authors.initials: DP
authors.lastname: Hartmann
authors.forename: Kamal
authors.initials: K
authors.lastname: Datta
authors.forename: Albert J
authors.initials: AJ
authors.lastname: Fornace
mesh_terms: D000236:Adenoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D005260:Female; D005720:Gamma Rays; D017491:Genes, APC; D020022:Genetic Predisposition to Disease / Q000235:genetics; D007414:Intestinal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D007420:Intestine, Large / Q000378:metabolism / Q000528:radiation effects; D007421:Intestine, Small / Q000378:metabolism / Q000528:radiation effects; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009381:Neoplasms, Radiation-Induced / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D011829:Radiation Dosage; D011960:Receptors, Estrogen / Q000378:metabolism; D012737:Sex Factors; D047368:Tumor Burden
chemical_list: D019394:Ki-67 Antigen; D011960:Receptors, Estrogen