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The effects of uranium exposure on human breast cancer cell lines MCF-7 and T-47D in vitro and in vivo

Enriquez, Desirae E (2021) The effects of uranium exposure on human breast cancer cell lines MCF-7 and T-47D in vitro and in vivo. Masters thesis, Northern Arizona University.

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Uranium (U) is a toxic and radioactive heavy metal that has significant uses in industry, fuel production and weapon manufacturing. Chronic U exposure may occur through routes such as inhalation, ingestion of contaminated food and water, and dermal exposure via interaction with contaminated soil and water. U concentrations in water resources have been found in urban and rural areas at and above the EPA limit, which puts citizens in those areas at higher risk of certain disease due to U toxicity. Some illnesses that are caused from U toxicity are: lung inflammation, lung abscess, renal tubular necrosis, organ damage and cancer. Breast cancer is a disease that affects 1 in 8 women over a course of their lifetime and has been known to be impacted by exposure to heavy metals. However, linkages between U exposure and breast cancer are weak. Uranium exposure may lead to carcinogenic outcomes through disruption of estrogenic pathways. To test if breast cancer proliferation is affected by U, we exposed MCF-7 and T-47D breast cancer cell lines in vitro and in vivo and assessed metabolism, viable DNA content per cell, and tumor growth area. Our results demonstrated that human breast cancer cells exposed to U, below the United States Environmental Protection Agency’s Maximum Exposure limit (MCL) for drinking water, responded with shifts in both viable DNA and cell proliferation in a dose and cell line-dependent fashion. Lower exposure concentrations induced proliferation; however, higher exposure concentrations reduced cell number. In addition, a zebrafish in vivo xenograft model demonstrated that low U exposure, again below the USEPA MCL, resulted in an increase in tumor area. In contrast to low U concentrations, high U concentration exposure led to a decrease in cell metabolism, viable DNA content and cell proliferation. In vivo results of high concentration U exposure resulted in no significant difference in tumor growth area. With this, our results demonstrate that human breast cancer cells respond non-monotonically to high and low U concentrations. Overall, these results signify the importance in understanding estrogenic pathways and the disruption of these pathways when environmental elements mask, inhibit or act like estrogen.

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: Breast Cancer; Estrogen; Receptors; Uranium; Uranyl Nitrate; Zebrafish
Subjects: Q Science > QP Physiology
MeSH Subjects: C Diseases > C25 Chemically-Induced Disorders
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: 02 Feb 2022 21:13
Last Modified: 02 Feb 2022 21:13
URI: https://openknowledge.nau.edu/id/eprint/5630

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