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dc.contributor.authorLu, Peter
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date.accessioned2019-09-24T20:22:35Z
dc.date.available2019-09-24T20:22:35Z
dc.identifier.urihttp://hdl.handle.net/1974/26601
dc.description.abstractIn utero exposure to benzene, a known carcinogenic environmental toxicant, is associated with the development of childhood leukemia. We have previously demonstrated that in utero exposure to benzene in CD-1 mice can alter the expression of the transcription factor NF-KB, which regulates genes involved in cell proliferation and programmed cell death, however, a full characterization of benzene’s effects on fetal NF-B is still needed. Since NF-KB regulates genes involved in cell proliferation, inappropriate activation can result in the proliferation of damaged cells potentially leading to the development of leukemia. We hypothesize that benzene metabolism in the maternal liver leads to fetal changes in NF-KB signalling. To test this hypothesis, pregnant CD-1 mice were exposed to 200 mg/kg benzene or its vehicle control on gestational days 8, 10, 12, and 14. Dams were sacrificed at 1, 2, 6, or 24 hours after the last benzene dose. Fetal livers were collected, and immunoblotting was done to assess changes in protein levels of phospho-p65, phospho-p38-MAPK, p50, and inhibitor of NF-KB (IKB-α). Results show that after in utero benzene exposure, protein levels of nuclear p50, phospho-p65 and phospho-p38-MAPK did not change significantly after benzene treatment but protein levels of IKB-α significantly increased 6 hours after the last benzene dose. However, there were no observed changes in the mRNA level of IKB-α. There were also no observed significant changes in the DNA binding activity of NF-KB following in utero benzene exposure. In conclusion, these results suggest that in utero benzene exposure does not alter NF-KB signalling in CD-1 mice fetal liver aside from the increased IKB-α protein levels. Further studies should be done using techniques that do not possess the limitations in this study.en_US
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsQueen's University's Thesis/Dissertation Non-Exclusive License for Deposit to QSpace and Library and Archives Canadaen
dc.rightsProQuest PhD and Master's Theses International Dissemination Agreementen
dc.rightsIntellectual Property Guidelines at Queen's Universityen
dc.rightsCopying and Preserving Your Thesisen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectLeukemiaen_US
dc.subjectWomen's Healthen_US
dc.subjectBenzeneen_US
dc.subjectChildren's healthen_US
dc.titleThe Effect of In Utero Benzene Exposure on Fetal NF-KB Cell Signalling in CD-1 Miceen_US
dc.typethesisen
dc.description.degreeMaster of Scienceen_US
dc.contributor.supervisorWinn, Louise M
dc.contributor.departmentBiomedical and Molecular Sciencesen_US
dc.embargo.termsThe data in this thesis will be incorporated into a peer-reviewed publication. We would like to collect more data before publication.en_US
dc.embargo.liftdate2024-09-23T14:57:39Z
dc.embargo.liftdate2024-09-24T02:34:35Z


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