title: Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation.
abstract: The human breast is sensitive to radiation carcinogenesis, and genomic instability occurs early in breast cancer development. This study tests the hypothesis that ionizing radiation elicits genomic instability in finite life-span human mammary epithelial cells (HMEC) and asks whether densely ionizing radiation is a more potent inducer of instability. HMEC in a non-proliferative state were exposed to X rays or 1 GeV/nucleon iron ions followed by delayed plating. Karyotypic instability and centrosome aberrations were monitored in expanded clonal isolates. Severe karyotypic instability was common in the progeny of cells that survived X-ray or iron-ion exposure. There was a lower dose threshold for severe karyotypic instability after iron-ion exposure. More than 90% of X-irradiated colonies and >60% of iron-ion-irradiated colonies showed supernumerary centrosomes at levels above the 95% upper confidence limit of the mean for unirradiated clones. A dose response was observed for centrosome aberrations for each radiation type. There was a statistically significant association between the incidence of karyotypic instability and supernumerary centrosomes for iron-ion-exposed colonies and a weaker association for X-irradiated colonies. Thus genomic instability occurs frequently in finite life-span HMEC exposed to sparsely or densely ionizing radiation and may contribute to radiation-induced breast cancer.
authors.affiliation: Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sudo
authors.forename: James
authors.initials: J
authors.lastname: Garbe
authors.forename: Martha R
authors.initials: MR
authors.lastname: Stampfer
authors.forename: Mary Helen
authors.initials: MH
authors.lastname: Barcellos-Hoff
authors.forename: Amy
authors.initials: A
authors.lastname: Kronenberg
mesh_terms: D017209:Apoptosis / Q000528:radiation effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000528:radiation effects*; D018385:Centrosome / Q000473:pathology* / Q000528:radiation effects*; D002869:Chromosome Aberrations / Q000528:radiation effects*; D004847:Epithelial Cells / Q000166:cytology / Q000528:radiation effects*; D020342:Finite Element Analysis; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D042361:Mammary Glands, Human / Q000166:cytology / Q000528:radiation effects*; D011839:Radiation, Ionizing