Date of Award

5-2017

Document Type

Honors Thesis

Degree Name

Bachelor of Science

Department

Biological Science

Advisor/Committee Chair

Melinda Larsen

Abstract

Arsenic is recognized as an environmental carcinogen, in which over 100 million individuals worldwide experience chronic exposure through contaminated drinking water. Arsenic exposure is linked to several health conditions, such as cancer, diabetes, skin lesions, immune dysfunction, and cardiovascular disease. Here we test the hypothesis that toxicants, such as arsenic, accelerate the program of senescence. Human (IMR-90) primary diploid fibroblasts were chronically exposed to arsenic at nanomolar concentrations and the impact on the expression of senescent-associated mRNAs was evaluated. IMR-90 cells were exposed either to untreated media or exposed to 130nM and 330nM AsCl3 supplemented media. RNA samples were extracted weekly from IMR-90 cells and RTPCR was conducted. Arsenic-exposed IMR-90 cells displayed increases in all senescence-associated transcripts monitored, those include Interleukin-6, Interleukin-8, Interleukin-alpha and the cyclin-dependent kinase inhibitor protein P16. At day 40, post AsCl3 exposure, a near 25-100 fold increase in senescent transcript expression was observed. Thus, there appears to be a direct relationship between the duration of toxicant stress, and the increased transcription level of senescent transcripts. Our studies suggest that low dose AsCl3 exposure promotes senescent transcript expression and very likely accelerates the senescent program that has the penitential of creating a cellular niche that is permissive to disease progression.

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