title: Intrachromosomal changes and genomic instability in site-specific microbeam-irradiated and bystander human-hamster hybrid cells.
abstract: Exposure to ionizing radiation may induce a heritable genomic instability phenotype that results in a persisting and enhanced genetic and functional change among the progeny of irradiated cells. Since radiation-induced bystander effects have been demonstrated with a variety of biological end points under both in vitro and in vivo conditions, this raises the question whether cytoplasmic irradiation or the radiation-induced bystander effect can also lead to delayed genomic instability. In the present study, we used the Radiological Research Accelerator Facility charged-particle microbeam for precise nuclear or cytoplasmic irradiation. The progeny of irradiated and the bystander human hamster hybrid (A(L)) cells were analyzed using multicolor banding (mBAND) to examine persistent chromosomal changes. Our results showed that the numbers of metaphase cells involving changes of human chromosome 11 (including rearrangement, deletion and duplication) were significantly higher than that of the control in the progeny of both nuclear and cytoplasmic targeted cells. These chromosomal changes could also be detected among the progeny of bystander cells. mBAND analyses of clonal isolates from nuclear and cytoplasm irradiations as well as the bystander cell group showed that chromosomal unstable clones were generated. Analyses of clonal stability after long-term culture indicated no significant change in the number of unstable clones for the duration of culture in each irradiated group. These results suggest that genomic instability that is manifested after ionizing radiation exposure is not dependent on direct damage to the cell nucleus.
authors.affiliation: Center for Radiological Research, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA. hubr@impcas.ac.cn
authors.forename: Burong
authors.initials: B
authors.lastname: Hu
authors.forename: Peter
authors.initials: P
authors.lastname: Grabham
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Adayabalam S
authors.initials: AS
authors.lastname: Balajee
authors.forename: Hongning
authors.initials: H
authors.lastname: Zhou
authors.forename: Tom K
authors.initials: TK
authors.lastname: Hei
authors.forename: Charles R
authors.initials: CR
authors.lastname: Geard
mesh_terms: D000818:Animals; D024201:Bystander Effect / Q000235:genetics* / Q000528:radiation effects*; D016466:CHO Cells; D002467:Cell Nucleus / Q000235:genetics / Q000528:radiation effects; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics* / Q000528:radiation effects*; D002999:Clone Cells / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D003593:Cytoplasm / Q000235:genetics / Q000528:radiation effects; D042822:Genomic Instability / Q000528:radiation effects*; D006801:Humans; D006822:Hybrid Cells / Q000166:cytology* / Q000378:metabolism / Q000528:radiation effects*; D013997:Time Factors
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