Document Type

Honors Thesis

Publication Date

Spring 5-2015

Abstract

Inorganic arsenic is a well-known toxic element found around the world, but the molecular mechanisms involved in arsenic toxicity are currently poorly understood. Arsenic has been linked to several types of cancer, diabetes, cardiovascular disease, and other metabolic diseases. This project explores the toxic effects of arsenic using mouse (Mus musculus) as a mammalian model organism. Preliminary data from the Van Beneden lab has shown that mice respond to low-dose, transplacental arsenic exposure in a dose-, sex-, and generation-dependent manner. The current study addresses a potential mechanism of toxicity by determining relative expression levels of pAKT/AKT1, a serine/threonine kinase that is activated via phosphorylation. In previous Van Beneden lab studies, arsenic exposure was linked to altered expression of several gene products that are involved in cell cycle regulation as well as glucose uptake and lipid transport; each of which is known to be regulated in part by AKT. Many of these pathways are highly conserved, making AKT the subject of a significant amount of cancer and diabetes research. We hypothesized a dose-dependent increase in pAKT/AKT expression, suggesting more AKT pathway activity in response to arsenic exposure. Initial data show a trend of reduced AKT activity at 50ppb and 500ppb transplacental arsenic exposure, but no sex- dependent response or statistically significant effects of the treatment levels. Analysis of pAKT/AKT expression provides insight to the molecular pathways involved in arsenic toxicology when partnered with existing literature and results of the ongoing study in the Van Beneden laboratory.

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