Honors College Thesis


Sulforaphane Regulation of LncRNA in a Transplacental Nrf2 Knockout Mouse Model Exposed to Dibenzo[def,p]chrysene Public Deposited

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  • Dibenzo[def,p]chrysene (DBC) is a highly potent, but less prevalent, environmental carcinogen belonging to a class of compounds known as Polycyclic Aromatic Hydrocarbons (PAHs). They are highly ubiquitous and arise as a byproduct of natural and anthropogenic combustion processes. Previous studies have documented carcinogenic effects upon in utero exposure of PAHs. Nuclear Factor Erythroid-2- Related Factor (Nrf2) is a transcription factor vital to the oxidative stress response. Consequently, Nrf2 deficiency in animal models has shown increased tumor incidence compared to those with Nrf2 when treated with an environmental carcinogen. Sulforaphane (SFN), a chemopreventive agent from cruciferous vegetables, induces phase II antioxidant genes via interaction with Nrf2. This enhances resistance to carcinogenesis. The primary objective of this study is to analyze the up or down regulation of various long non-coding RNA (lncRNA >200bp) utilizing a Nrf2 Knockout Mouse Model. LncRNA have been found to possess a myriad of functions as molecular signals and molecular decoys that move to activate and suppress gene expression. They have the ability to guide ribonucleoprotein complexes to assemble at specific chromatin sites. Consequently, cis or trans gene expression is induced. LncRNA regulation will be evaluated in lung tissue from adult offspring exposed in utero to sulforaphane. Sulforaphane was used as a dietary chemopreventive agent in some treatment groups to compare tumor incidence in 10-month old adult offspring. This phytochemical was exposed to the fetus transplacentally and through lactational exposure. The two treatment groups utilized are as follow: control lung from adult offspring; lung from adult offspring born to mothers given a sulforaphane diet. A commercially available LncProfiler RT-qPCR array (System Biosciences, Mountain View, CA. #RA930A-1) was used to examine the lncRNA profiles of the treatment group relative to the control. This study is being conducted in efforts to document a potential correlation between fetal exposure to PAHs, abundance of cancer associated lncRNA and the impact of the Nrf2 genotype in the presence of the prototypical Nrf2 agonist, sulforaphane.
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