title: Induction of genetic instability by transfer of a UV-A-irradiated chromosome.
abstract: Exposure of cells to ultraviolet (UV)-A radiation induces oxidative damage in DNA, such as 8-oxo-7,8-dihydroguanine (8-oxoG), single-strand breaks, a-basic sites, and DNA-protein cross-links, via reactions with reactive oxygen species (ROS). In this study we examine whether the damage other than double-strand breaks (non-DSB damage), which is UV-A-induced oxidative damage, plays a role in the induction of chromosomal instability. We exposed human chromosome 21 to UV-A and transferred the chromosome into non-irradiated mouse recipient cells by microcell-mediated chromosome transfer. The chromosomal instability of both the transferred human chromosome and the recipient mouse chromosomes was examined by whole-chromosome painting and fluorescence in situ hybridization (WCP-FISH). The ploidy of the mouse recipient cells increased, and chromosomal aberrations occurred not only in the UV-A-irradiated human chromosome but also in the non-irradiated mouse chromosomes. The frequencies of these abnormalities increased with the radiation dose received by the transferred human chromosome. In contrast, in the control experiment, in which an non-irradiated human chromosome was transferred, the micro-cell hybrids remained diploid, and the frequency of chromosomal aberrations in both the transferred human chromosome and recipient mouse chromosomes remained low. Thus, the present study indicates that a chromosome harboring non-DSB damage induced by UV-A irradiation is unstable and transmits instability to chromosomes of non-irradiated recipient mouse cells.
authors.affiliation: Advanced Research Science Centre, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai-mura, Ibaraki, Ibaraki 319-1195, Japan; Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Nakaku, Sakai, Osaka 599-8570, Japan. Electronic address: urushibara.ayumi@gmail.com.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Urushibara
authors.affiliation: Laboratory of Radiation Biology, Department of Biological Science, Graduate School of Science, Osaka Prefecture University, 1-2 Gakuen-cho, Nakaku, Sakai, Osaka 599-8570, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Kodama
authors.affiliation: Advanced Research Science Centre, Japan Atomic Energy Agency, 2-4 Shirakata-Shirane, Tokai-mura, Ibaraki, Ibaraki 319-1195, Japan.
authors.forename: Akinari
authors.initials: A
authors.lastname: Yokoya
mesh_terms: D000818:Animals; D002460:Cell Line; D002869:Chromosome Aberrations / Q000528:radiation effects*; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics* / Q000378:metabolism; D053904:DNA Breaks, Single-Stranded; D042822:Genomic Instability / Q000528:radiation effects*; D006151:Guanosine / Q000031:analogs & derivatives / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D006151:Guanosine; C046215:8-hydroxyguanosine
keywords: Chromosomal aberration; Chromosomal instability; DNA damage; Microcell-mediated chromosome transfer; Polyploidy; UV-A