title: Microarray analysis of differentially expressed genes in the kidneys and testes of mice after long-term irradiation with low-dose-rate gamma-rays.
abstract: Measuring global gene expression using cDNA or oligonucleotide microarrays is an effective approach to understanding the complex mechanisms of the effects of radiation. However, few studies have been carried out that investigate gene expression in vivo after prolonged exposure to low-dose-rate radiation. In this study, C57BL/6J mice were continuously irradiated with gamma-rays for 485 days at dose-rates of 0.032-13 microGy/min. Gene expression profiles in the kidney and testis from irradiated and unirradiated mice were analyzed, and differentially expressed genes were identified. A combination of pathway analysis and hierarchical clustering of differentially expressed genes revealed that expression of genes involved in mitochondrial oxidative phosphorylation was elevated in the kidney after irradiation at the dose-rates of 0.65 microGy/min and 13 microGy/min. Expression of cell cycle-associated genes was not profoundly modulated in the kidney, in contrast to the response to acute irradiation, suggesting a threshold in the dose-rate for modulation of the expression of cell cycle-related genes in vivo following exposure to radiation. We demonstrated that changes to the gene expression profile in the testis were largely different from those in the kidney. The Gene Ontology categories "DNA metabolism", "response to DNA damage" and "DNA replication" overlapped significantly with the clusters of genes whose expression decreased with an increase in the dose-rate to the testis. These observations provide a fundamental insight into the organ-specific responses to low-dose-rate radiation.
authors.affiliation: Radiation Effect Mechanisms Research Group, National Institute of Radiological Sciences, 9-1 Anagawa-4-chome, Inage-ku, Chiba, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Taki
authors.forename: Bing
authors.initials: B
authors.lastname: Wang
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Nakajima
authors.forename: Jianyu
authors.initials: J
authors.lastname: Wu
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Ono
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Uehara
authors.forename: Tsuneya
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Oghiso
authors.forename: Kimio
authors.initials: K
authors.lastname: Tanaka
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Ichinohe
authors.forename: Shingo
authors.initials: S
authors.lastname: Nakamura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tanaka
authors.forename: Junji
authors.initials: J
authors.lastname: Magae
authors.forename: Ayana
authors.initials: A
authors.lastname: Kakimoto
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Nenoi
mesh_terms: D000818:Animals; D004307:Dose-Response Relationship, Radiation; D005720:Gamma Rays; D005786:Gene Expression Regulation; D007668:Kidney / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D046228:Microarray Analysis; D011827:Radiation; D013737:Testis / Q000378:metabolism*