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Identification of ribonucleic acid splicing defect and oxidative stress-inducing environmental chemicals in Caenorhabditis elegans

dc.contributor.committeeMemberJanz, David
dc.contributor.committeeMemberBrinkmann, Markus
dc.contributor.committeeMemberUnniappan, Suraj
dc.contributor.committeeMemberWu, Michael`
dc.creatorHuynh, Dylan V
dc.creator.orcid0000-0002-1608-1496
dc.date.accessioned2022-09-15T19:31:21Z
dc.date.available2022-09-15T19:31:21Z
dc.date.copyright2022
dc.date.created2022-11
dc.date.issued2022-09-15
dc.date.submittedNovember 2022
dc.date.updated2022-09-15T19:31:21Z
dc.description.abstractRibonucleic acid (RNA) splicing removes non-coding regions of deoxyribonucleic acid (DNA) from a transcribed messenger RNA (mRNA) strand which is required for gene expression. RNA splicing is catalyzed by the spliceosome which is a complex of small nuclear RNAs (snRNAs) as well as many proteins. RNA splicing is also indirectly catalyzed by the processing of snRNAs by a protein complex called the integrator. Environmental contaminants such as cadmium can induce splicing errors, suggesting that RNA splicing defects can be induced by chemical exposure. In the first study, the model organism C. elegans was screened against the United States Environmental Protection Agency (U.S. EPA) ToxCast Screening Library containing 4665 chemicals for environmental chemicals that induce RNA splicing defects. This screen identified 108 chemicals that potentially induced RNA splicing defects. One of those chemicals, pararosaniline hydrochloride was selected for further study, including its effects on C. elegans physiology including development, reproduction, and aging. Quantitative PCR (qPCR) was used to confirm the induction of RNA splicing defects. Overall, this study identified new RNA splicing defect-inducing chemicals in our environment that are likely to exhibit cellular toxicity. Oxidative stress can result from an imbalance between the production of reactive oxygen species (ROS) and the three-phase detoxification system. The damage caused by oxidative stress is linked to various human diseases such as atherosclerosis, diabetes, as well as neurodegenerative syndromes and aging. ROS can be produced by the metabolism of toxic or reactive compounds which is part of the three-phase detoxification system. Phase I enzymes converts the xenobiotic into metabolites that is then solubilized by phase II enzymes prior to excretion by phase III transporters. In the second study, C. elegans was screened against the U.S. EPA ToxCast Screening Library for environmental chemicals that induce an oxidative stress response. This screen identified 59 chemicals that potentially inducde an oxidative stress response. qPCR was used to confirm the induction of oxidative stress for the top 10 chemicals. Overall, this study identified new oxidative stress-inducing chemicals in our environment that are likely to exhibit cellular toxicity.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttps://hdl.handle.net/10388/14168
dc.language.isoen
dc.subjectRNA splicing
dc.subjectoxidative stress
dc.subjectCaenorhabditis elegans
dc.subjectU.S. EPA ToxCast Screening Library
dc.subjectHigh-throughput screen
dc.titleIdentification of ribonucleic acid splicing defect and oxidative stress-inducing environmental chemicals in Caenorhabditis elegans
dc.typeThesis
dc.type.materialtext
thesis.degree.departmentVeterinary Biomedical Sciences
thesis.degree.disciplineVeterinary Biomedical Sciences
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (M.Sc.)

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