title: Micronuclei formation induced by X-ray irradiation does not always result from DNA double-strand breaks.
abstract: X-ray induced formation of micronuclei is generally thought to result from DNA double-strand breaks (DSBs). However, DNA DSBs inhibit the cell cycle progression that is required for micronucleus formation. In order to reconcile this apparent discrepancy, we investigated whether DNA DSBs induced during the G1 phase could lead to micronucleus formation. We irradiated human embryonic (HE17) cells that had been treated with a radical scavenger, either DMSO or ascorbic acid (AsA), and determined the level of suppression of DNA DSBs or micronuclei. When DNA DSBs were evaluated using 53BP1 foci, treatment with 5 mM AsA did not inhibit the numbers of foci at various intervals after X-ray irradiation; however, treatment with 5 mM or 256 mM DMSO did have a significant inhibitory effect. By contrast, an assay of micronucleus numbers showed that treatment with 5 mM or 256 mM DMSO before X-ray irradiation resulted in almost no inhibition of micronucleus formation, but treatment with 5 mM AsA did have a significant inhibitory effect. These results clearly showed that AsA could suppress micronucleus formation, although it was not effective for suppression of DNA DSBs. Therefore, we conclude that DNA DSBs induced in the G1 phase do not directly lead to micronucleus formation.
authors.affiliation: Laboratory of Radiation Biology, Research Reactor Institute, Kyoto University, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Okada
authors.forename: Genro
authors.initials: G
authors.lastname: Kashino
authors.forename: Hideki
authors.initials: H
authors.lastname: Nishiura
authors.forename: Keizo
authors.initials: K
authors.lastname: Tano
authors.forename: Masami
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D016923:Cell Death; D002478:Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D020090:Chromosome Segregation / Q000528:radiation effects*; D003114:Colony-Forming Units Assay; D004247:DNA / Q000187:drug effects / Q000528:radiation effects*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D003864:Depression, Chemical; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology; D016166:Free Radical Scavengers / Q000494:pharmacology; D005609:Free Radicals; D016193:G1 Phase / Q000528:radiation effects*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015162:Micronucleus Tests; D008957:Models, Genetic
chemical_list: D016166:Free Radical Scavengers; D005609:Free Radicals; D004247:DNA; D001205:Ascorbic Acid; D004121:Dimethyl Sulfoxide