title: In vivo bystander effect: cranial X-irradiation leads to elevated DNA damage, altered cellular proliferation and apoptosis, and increased p53 levels in shielded spleen.
abstract: OBJECTIVE
  It is well accepted that irradiated cells may "forward" genome instability to nonirradiated neighboring cells, giving rise to the "bystander effect" phenomenon. Although bystander effects were well studied by using cell cultures, data for somatic bystander effects in vivo are relatively scarce.
  
  
  METHODS
  We set out to analyze the existence and molecular nature of bystander effects in a radiation target-organ spleen by using a mouse model. The animal's head was exposed to X-rays while the remainder of the body was completely protected by a medical-grade shield. Using immunohistochemistry, we addressed levels of DNA damage, cellular proliferation, apoptosis, and p53 protein in the spleen of control animals and completely exposed and head-exposed/body bystander animals.
  
  
  RESULTS
  We found that localized head radiation exposure led to the induction of bystander effects in the lead-shielded distant spleen tissue. Namely, cranial irradiation led to increased levels of DNA damage and p53 expression and also altered levels of cellular proliferation and apoptosis in bystander spleen tissue. The observed bystander changes were not caused by radiation scattering and were observed in two different mouse strains; C57BL/6 and BALB/c.
  
  
  CONCLUSIONS
  Our study proves that bystander effects occur in the distant somatic organs on localized exposures. Additional studies are required to characterize the nature of an enigmatic bystander signal and analyze the long-term persistence of these effects and possible contribution of radiation-induced bystander effects to secondary radiation carcinogenesis.
authors.affiliation: Department of Biological Sciences, University of Lethbridge, Alberta, Canada.
authors.forename: Igor
authors.initials: I
authors.lastname: Koturbash
authors.forename: Jonathan
authors.initials: J
authors.lastname: Loree
authors.forename: Kristy
authors.initials: K
authors.lastname: Kutanzi
authors.forename: Clayton
authors.initials: C
authors.lastname: Koganow
authors.forename: Igor
authors.initials: I
authors.lastname: Pogribny
authors.forename: Olga
authors.initials: O
authors.lastname: Kovalchuk
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D024201:Bystander Effect / Q000502:physiology*; D049109:Cell Proliferation / Q000528:radiation effects*; D016371:Cranial Irradiation; D004247:DNA / Q000528:radiation effects; D004249:DNA Damage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011835:Radiation Protection; D013154:Spleen / Q000166:cytology / Q000378:metabolism / Q000503:physiopathology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
chemical_list: D016159:Tumor Suppressor Protein p53; D004247:DNA