title: Prolonged expression of senescence markers in mice exposed to gamma-irradiation.
abstract: Although ionizing radiation is known to induce cellular senescence in vitro and in vivo, its long-term in vivo effects are not well defined. In this study, we examined the prolonged expression of senescence markers in mice irradiated with single or fractionated doses. C57BL/6 female mice were exposed to 5 Gy of γ-rays in single or 5, 10, 25 fractions. At 2, 4, and 6 months after irradiation, senescence markers including mitochondrial DNA (mtDNA) common deletion, p21, and senescence-associated β-galactosidase (SA β-gal) were monitored in the lung, liver, and kidney. Increases of mtDNA deletion were detected in the lung, liver, and kidney of irradiated groups. p21 expression and SA β-gal staining were also increased in the irradiated groups compared to the non irradiated control group. Increases of senescence markers persisted up to 6 months after irradiation. Additionally, the extent of mtDNA deletion and the numbers of SA β-gal positive cells were greater as the number of radiation fractions increased. In conclusion, our results showed that ionizing radiation, especially that delivered in fractions, can cause the persistent upregulation of senescence marker expression in vivo. This should be considered when dealing with chronic normal tissue injuries caused by radiation therapy or radiation accidents.
authors.affiliation: Radiation Biotechnology Research Division, Advanced Radiation Technology Institute, Korea Atomic Energy Research Institute, Jeongeup 580-185, Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Seol
authors.forename: Uhee
authors.initials: U
authors.lastname: Jung
authors.forename: Hyeon Soo
authors.initials: HS
authors.lastname: Eom
authors.forename: Seol-Hwa
authors.initials: SH
authors.lastname: Kim
authors.forename: Hae-Ran
authors.initials: HR
authors.lastname: Park
authors.forename: Sung-Kee
authors.initials: SK
authors.lastname: Jo
mesh_terms: D000367:Age Factors; D000818:Animals; D015153:Blotting, Western; D016922:Cellular Senescence / Q000528:radiation effects*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D005260:Female; D005720:Gamma Rays; D017353:Gene Deletion; D005786:Gene Expression Regulation / Q000528:radiation effects*; D005819:Genetic Markers / Q000235:genetics*; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; D017931:DNA Primers; D004272:DNA, Mitochondrial; D005819:Genetic Markers; D001616:beta-Galactosidase