Karyotypic instability and centrosome aberrations in the progeny of finite life-span human mammary epithelial cells exposed to sparsely or densely ionizing radiation.
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.
Sudo
Hiroko
H
Life Science Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA.
Garbe
James
J
Stampfer
Martha R
MR
Barcellos-Hoff
Mary Helen
MH
Kronenberg
Amy
A
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