title: Genetic factors influencing bystander signaling in murine bladder epithelium after low-dose irradiation in vivo.
abstract: Radiation-induced bystander effects occur in cells that are not directly hit by radiation tracks but that receive signals from hit cells. They are well-documented in vitro consequences of low-dose exposure, but their relevance to in vivo radiobiology is not established. To investigate the in vivo production of bystander signals, bladder explants were established from two strains of mice known to differ significantly in both short-term and long-term radiation responses. These were investigated for the ability of 0.5 Gy total-body irradiation in vivo to induce production of bystander signals in bladder epithelium. The studies demonstrate that irradiated C57BL/6 mice, but not CBA/Ca mice, produce bystander signals that induce apoptosis and reduce clonogenic survival in reporter HPV-G-transfected keratinocytes. Transfer of medium from explants established from irradiated animals to explants established from unirradiated animals confirmed these differences in bladder epithelium. The responses to the in vivo-generated bystander signal exhibit genotypic differences in calcium signaling and also in signaling pathways indicative of a major role for the balance of pro-apoptosis and anti-apoptosis proteins in determining the overall response. The results clearly demonstrate the in vivo induction of bystander signals that are strongly influenced by genetic factors and have implications for radiation protection, medical imaging, and radiotherapy.
authors.affiliation: Radiation and Environmental Science Centre, Dublin Institute of Technology, Dublin, Ireland. mothers@mcmaster.ca
authors.forename: Carmel
authors.initials: C
authors.lastname: Mothersill
authors.forename: Fiona
authors.initials: F
authors.lastname: Lyng
authors.forename: Colin
authors.initials: C
authors.lastname: Seymour
authors.forename: Paula
authors.initials: P
authors.lastname: Maguire
authors.forename: Sally
authors.initials: S
authors.lastname: Lorimore
authors.forename: Eric
authors.initials: E
authors.lastname: Wright
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D024201:Bystander Effect / Q000235:genetics* / Q000528:radiation effects*; D002118:Calcium / Q000378:metabolism*; D004848:Epithelium / Q000502:physiology / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D011829:Radiation Dosage; D011836:Radiation Tolerance / Q000235:genetics*; D013045:Species Specificity; D001743:Urinary Bladder / Q000502:physiology* / Q000528:radiation effects*; D014916:Whole-Body Irradiation / Q000379:methods
chemical_list: D002118:Calcium