• Login
    View Item 
    •   Home
    • University of Alaska Fairbanks
    • UAF Graduate School
    • Older Theses Not Clearly Affiliated with a Current College
    • View Item
    •   Home
    • University of Alaska Fairbanks
    • UAF Graduate School
    • Older Theses Not Clearly Affiliated with a Current College
    • View Item
    JavaScript is disabled for your browser. Some features of this site may not work without it.

    Browse

    All of Scholarworks@UACommunitiesPublication DateAuthorsTitlesSubjectsTypeThis CollectionPublication DateAuthorsTitlesSubjectsType

    My Account

    Login

    First Time Submitters, Register Here

    Register

    Statistics

    Display statistics

    DNA mismatch repair at an oncogenic hotspot correlated with phase of the cell cycle and environmentally relevant concentrations of the Arctic pollutant p, p'-DDE

    • CSV
    • RefMan
    • EndNote
    • BibTex
    • RefWorks
    Thumbnail
    Name:
    Simonetti.Josephine.2001.pdf
    Size:
    2.999Mb
    Format:
    PDF
    Download
    Author
    Simonetti, Josephine
    Metadata
    Show full item record
    URI
    http://hdl.handle.net/11122/5031
    Abstract
    Part I: Mismatch repair in G₁ synchronized mammalian cells. Deficiencies in DNA mismatch repair have been found in hereditary nonpolyposis colon cancer (HNPCC), as well as in sporadic cancers, illustrating the importance of this single repair system in maintaining genomic integrity. In bacteria, this repair system functions primarily, after DNA replication, in the correction of polymerase base insertion errors and in mammalian cells it was also assumed that the mismatch repair system functioned within a similar timeframe. However, DNA mismatches occur ubiquitously and their repair before DNA replication is of paramount importance for faithful genome copying. We investigated the activity of the mismatch repair system, in G₁ synchronized NIH 3T3 cells, in the repair of four mismatches at an oncogenic hotspot in the H-ras gene. Our results clearly show that the mismatch repair system is active and accurate during the pre-replicative G₁ phase of the mammalian cell cycle. Part II: Effects of p, p'-DDE on cell toxicity and DNA mismatch repair ability. Umbilical cord blood, from Inupiat infants in Barrow Alaska, was examined for the presence of several environmental contaminants. All 24 blood samples analyzed contained measurable levels of p, p'-DDE (1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene) with an average concentration of 0.33 ug/1. We examined whether this low concentration of p, p'-DDE had detectable effects on NIH 3T3 (mouse embryonic) and WS1 (human fetal) cells in culture. Initial experiments indicated that exposure to p, p'-DDE resulted in a decrease in the cell number of both cell types. Subsequent analysis revealed that this decrease was due to cell death in NIH 3T3 cells and to cell cycle arrest in WS1 cells. We also examined the effect of p, p'-DDE on the ability of both cell types to repair mismatches at an oncogenic hotspot in H-ras. Preliminary results indicate that p, p'-DDE does not have a discernable effect on the ability of either cell type to correctly repair the G:T mismatch. However, p, p'-DDE exposure results in an increased rate of correct repair of the G:A mismatch by both cell types. Overall, this study demonstrates that p, p'-DDE, at concentrations relevant to the Alaskan environment has significantn but different effects on two immature cell types in culture.
    Description
    Dissertation (Ph.D.) University of Alaska Fairbanks, 2001
    Date
    2001-05
    Type
    Dissertation
    Collections
    Theses (Unassigned)
    Older Theses Not Clearly Affiliated with a Current College

    entitlement

     
    ABOUT US|HELP|BROWSE|ADVANCED SEARCH

    The University of Alaska Fairbanks is an affirmative action/equal opportunity employer and educational institution and is a part of the University of Alaska system.

    ©UAF 2013 - 2023 | Questions? ua-scholarworks@alaska.edu | Last modified: September 25, 2019

    Open Repository is a service operated by 
    Atmire NV
     

    Export search results

    The export option will allow you to export the current search results of the entered query to a file. Different formats are available for download. To export the items, click on the button corresponding with the preferred download format.

    By default, clicking on the export buttons will result in a download of the allowed maximum amount of items.

    To select a subset of the search results, click "Selective Export" button and make a selection of the items you want to export. The amount of items that can be exported at once is similarly restricted as the full export.

    After making a selection, click one of the export format buttons. The amount of items that will be exported is indicated in the bubble next to export format.