Radiation-induced bystander effects in vivo are sex specific.
Ionizing radiation (IR) effects span beyond the area of direct exposure and can be observed in neighboring and distant naïve cells and organs. This phenomenon is termed a 'bystander effect'. IR effects in directly exposed tissue in vivo are epigenetically mediated and distinct in males and females. Yet, IR-induced bystander effects have never been explored in a sex-specificity domain. We used an in vivo mouse model, whereby the bystander effects are studied in spleen of male and female animals subjected to head exposure when the rest of the body is protected by a medical-grade lead shield. We analyzed the induction of DNA damage and alterations in global DNA methylation. Molecular parameters were correlated with cellular proliferation and apoptosis levels. The changes observed in bystander organs are compared to the changes in unexposed animals and animals exposed to predicted and measured scatter doses. We have found the selective induction of DNA damage levels, global DNA methylation, cell proliferation and apoptosis in exposed and bystander spleen tissue of male and female mice. Sex differences were significantly diminished in animals subjected to a surgical removal of gonads. These data constitute the first evidence of sex differences in radiation-induced bystander effects in mouse spleen in vivo. We show the role of sex hormones in spleen bystander responses and discuss implications of the observed changes.
Department of Biological Sciences, University of Lethbridge, Alberta, Canada.
Igor
I
Koturbash
Kristy
K
Kutanzi
Karl
K
Hendrickson
Rocio
R
Rodriguez-Juarez
Dmitry
D
Kogosov
Olga
O
Kovalchuk
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects; D024201:Bystander Effect; D049109:Cell Proliferation / Q000528:radiation effects; D004249:DNA Damage / Q000528:radiation effects; D019175:DNA Methylation; D005260:Female; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011836:Radiation Tolerance; D011839:Radiation, Ionizing; D012727:Sex Characteristics; D013154:Spleen
C497393:Mecp2 protein, mouse; D051783:Methyl-CpG-Binding Protein 2