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Effects of acute noise exposure on DNA damage response genes in the cochlea, cortex, heart and liver

Yang, Li (2018) Effects of acute noise exposure on DNA damage response genes in the cochlea, cortex, heart and liver. Masters thesis, Northern Arizona University.

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Background: Noise as a systemic stressor induces various organ dysfunctions and the underlying molecular pathology is unknown. However, noise exposure results in the accumulation of DNA damage in auditory and non-auditory organs, which implicates molecular mechanisms of DNA damage and repair. The DNA damage response (DDR) is a global protective mechanism that plays a critical role in maintaining DNA integrity. Previous research has revealed that chronic noise exposure alters the normal expression pattern of DDR genes in the auditory system and this alteration is associated with permanent sensorineural hearing loss. Hypothesis: The role of DDR genes in noise induced systemic (non-auditory) pathology has not been investigated. For instance, it is known that noise exposure results in the accumulation of damaged DNA within the cortex, heart and liver, yet it is not known whether or not DDR genes are mobilized within these organs due to noise exposure. The current pilot study was designed to test the hypothesis that an acute noise exposure would alter the normal expression of DDR genes (e.g., ATM, p53 & XPC) in auditory (cochlea) and non-auditory organs, such as the cortex, heart and liver. Methods: Mice were used as subjects in this study and consisted of a baseline group, a one hour noise exposure group, and a four hour noise exposure group. Each group of mice were sacrificed for organ harvest at each of the three time points. The organs consisted of cochlea, cortex, heart and liver. Purification and quantification of total RNA was conducted from each organ. Messenger RNA was reverse transcribed to cDNA. The cDNA products were quantified and served as templates for end-point polymerase chain reactions (PCR). These PCR products were then loaded onto 1.5% agarose for gel electrophoresis. The electrophoresis bands were then processed for semi-quantification and statistical analysis. Results: Acute noise exposure failed to elicit statistically significant changes in DDR genes (relative to baseline) across the various organs. Conclusions: The failure of the cochlea, heart, cortex and liver to upregulate protective DDR genes during acute noise exposure might help to explain their susceptibility to noise-induced DNA damage. This suggest that, biomedical interventions to upregulate DDR genes may need to be implemented before noise exposure or during the early stages of noise exposure.

Item Type: Thesis (Masters)
Publisher’s Statement: © Copyright is held by the author. Digital access to this material is made possible by the Cline Library, Northern Arizona University. Further transmission, reproduction or presentation of protected items is prohibited except with permission of the author.
Keywords: Cochlea; Cortex; DDR genes; Heart; Liver; Noise exposure; DNA damage response;
Subjects: R Medicine > RC Internal medicine
MeSH Subjects: G Phenomena and Processes > G01 Physical Phenomena
NAU Depositing Author Academic Status: Student
Department/Unit: Graduate College > Theses and Dissertations
College of the Environment, Forestry, and Natural Sciences > Biological Sciences
Date Deposited: 21 Feb 2022 17:39
Last Modified: 21 Feb 2022 21:43
URI: https://openknowledge.nau.edu/id/eprint/5295

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