Investigating a Role for Mismatch Repair in Activating a Benzo[a]pyrene Diol Epoxide-InducedS-phase Checkpoint Public Deposited

Investigating a Role for DNA Mismatch Repair in Signaling a Benzo[a]pyrene Diol Epoxide-Induced DNA Replication Arrest

http://ir.library.oregonstate.edu/concern/undergraduate_thesis_or_projects/pr76f5108

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  • Genetic and environmental factors influence individual cancer risk. Mutations in DNA mismatch repair (MMR) genes increase colon cancer risk. Exposure to carcinogens, including the ubiquitous polycyclic aromatic hydrocarbons (PAHs), also is associated with increased cancer risk. To understand the combined effects of both environmental exposures and genetic risk, we investigated a role for MMR in cellular responses to PAHs. Benzo[a]pyrene (BaP) is a much-studied carcinogenic PAH; once metabolized to the diol epoxide (BPDE), it forms DNA adducts, which block DNA replication. This disruption signals for cell growth arrest, allows for adduct removal, and prevents accumulation of mutations. One of the first signaling events in cell growth arrest is the phosphorylation of the Chk1 kinase. To determine whether MMR deficiency influences BPDE-induced cell-cycle arrest, we measured increased phosphorylation of Chk1 in response to BPDE in MMR-proficient and -deficient human cell lines by immunoblotting. Preliminary data suggested sustained S-phase checkpoint in MMR-deficient cells relative to MMR-proficient cells. We also used flow cytometry to measure S-phase checkpoint activation. However, due to either technical or biological issues, or a combination, we could not find consistent patterns in cellular response to BPDE exposure in the two cell lines with either method.
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  • description.provenance : Submitted by Wanda Crannell (brr@oregonstate.edu) on 2012-12-17T18:29:22ZNo. of bitstreams: 2Jacki Coburn Thesis Presentation (2).pdf: 1763120 bytes, checksum: ddcdcf50f1dd050eb521866c0e17f2cd (MD5)Jacki Coburn Thesis Revised.pdf: 1032128 bytes, checksum: bd004f54dea7e3231c24aeee05c77d4f (MD5)
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