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Variation in chromosomal aberration induction in differing ATM and ASPM genotypic backgrounds detected via a modified PNA FISH technique

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dc.contributor.authorRomero, Ashley, author
dc.contributor.authorKato, Takamitsu, advisor
dc.contributor.authorBedford, Joel, committee member
dc.contributor.authorThamm, Douglas, committee member
dc.date.accessioned2007-01-03T05:56:52Z
dc.date.available2007-01-03T05:56:52Z
dc.date.issued2013
dc.description.abstractA modified PNA (peptide nucleic acid) FISH (fluorescence in situ hybridization) method has been developed for efficient quantitative and qualitative analysis of chromosomal aberration formation. PNA FISH was used to detect a heightened sensitivity in mouse fibroblasts in response to ionizing radiation with Atm-/- and in mouse embryonic fibroblasts (MEFs) in response to loss of Aspm gene respectively. For Atm analysis, four commonly used inbred mouse strains were used, C57BL/6J, A/J, 129S6, and BALB/cByJ, and exposed to cesium-137 at a dose rate of approximately 2.5 Gy/min. For Aspm analysis, MEF cell lines were used and exposed to 0.2 μM tamoxifen for inducible Cre-lox excision of floxed Aspm alleles. Upon analysis of chromosome-type aberrations, there were statistically significant elevations in acentric fragment and/or dicentric average frequencies seen across all strain backgrounds of the Atm-/- genotype, however, only the 129S6 Atm-/- strain backgrounds exhibited a significant increase in mean telomere-associated fusion events. In addition, there was a heightened dose response from a 0 to 2 Gy dose in Atm-/- BALB/cByJ and C57BL/6J backgrounds indicating a lack of synergism of the Prkdc (protein kinase, DNA-activated, catalytic polypeptide) defect in BALB/cByJ strains. For Aspm analysis, in comparison to control, or untreated, MEF strains, there was an increased average aberration frequency in Aspm-/- cell lines over a 48-hour time period. However, there was also an increased frequency in Aspm+/- cell lines comparable to the frequency observed in Aspm-/- cells, which is characteristic of haploinsufficiency. Therefore, not only is Atm status an important determinant of radiosensitivity, but strain backgrounds can also contribute to a heightened response. In addition, Aspm expression is critical for the maintenance and repair of DNA. Together, this data suggests that the Atm and Aspm genes are crucial components in the preservation of chromosomal integrity and genomic stability in response to DNA damage.
dc.format.mediumborn digital
dc.format.mediummasters theses
dc.identifierRomero_colostate_0053N_11871.pdf
dc.identifier.urihttp://hdl.handle.net/10217/80307
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2000-2019
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.subjectaberration
dc.subjectPNA FISH
dc.subjectchromosome
dc.subjectATM
dc.subjectASPM
dc.titleVariation in chromosomal aberration induction in differing ATM and ASPM genotypic backgrounds detected via a modified PNA FISH technique
dc.typeText
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineEnvironmental and Radiological Health Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.S.)

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