Long-term exposure to harmful carcinogens like benzo[a]pyrene (BaP) are linked to lung cancer. Benzo[a]pyrene diol epoxide (BPDE), the ultimate carcinogen produced by BaP bioactivation, is believed to play an important role in lung carcinogenesis....
N-acetyltransferase 1 (NAT1) is a phase II metabolic enzyme responsible for the biotransformation of aromatic and heterocyclic amine carcinogens such as 4-aminobiphenyl (ASP). NAT1 catalyzes N-acetylation of arylamines as well as the 0-acetylation...
Nerves--Regeneration; Spinal cord--Wounds and injuries--Treatment
These studies set out to identify strategies to rescue and repair the adult nervous system. First, we investigated the role of ciliary neurotrophic factor (CNTF) in 5HT1A receptor-induced neurogenesis in the rodent brain. Systemic treatment with an...
Green tea--Health aspects; Green tea--Therapeutic use; Polyphenols--Physiological effect; Drug delivery systems; Lungs--Cancer--Treatment
Green tea polyphenols (GTPs) are gaining increasing attention because of their potential anti-tumor effects. However, poor oral bioavailability limits their efficacy in vivo. In this dissertation, two hypotheses were tested: 1) GTPs administered...
Hepatitis C virus--Research; Interferon--Therapeutic use; Adenosylmethionine
Hepatitis C virus (HCV) infection is a major cause of chronic liver disease in the United States and is a huge burden on the US healthcare system. The FDA-approved traditional standard of care for HCV is pegylated interferon-alpha (lFNα) combined...
Sulforaphane (SFN), an isothiocyanate found in cruciferous vegetables, is known to confer antioxidant protection in vivo. Rather than directly reacting with free radicals, however, SFN works by inducing Nrf2, a transcription factor that binds to...
Polychlorinated biphenyls (PCBs) are persistent environmental pollutants which
are detectable in the serum of all American adults. Amongst PCB congeners,
PCB 153 has the highest serum level. PCBs have been dose-dependently
associated with suspected...
Xenoestrogens are spread throughout the environment affecting our daily
lives and may produce potential toxic effects on human health. The purpose of
this study was to develop a mechanistically reliable model capable of identifying
xenoestrogens....
Alcoholic liver disease (ALD) ranks among the major causes of morbidity and mortality in the world and effects millions of patients each year. Progression of ALD is well characterized and is actually a spectrum of liver diseases, which progresses...
Human arylamine N-acetyltransferase (NAT) is a phase II cytosolic enzyme that occurs as two isozymes, NAT1 and NAT2. This family of polymorphic enzymes catalyzes the detoxification and/or activation of many aromatic and heterocyclic amine drugs and...
Pancreatic beta cells are extremely vulnerable to the destruction of Reactive Oxygen Species (ROS). In both type 1 and type 2 diabetes ROS are involved in the loss of U+000DF-cells. We hypothesized that the deficiency in ROS detoxifying system of...
This thesis begins by reviewing human N-acetyltransferases (Chapter I), then outlines experiments involving human hepatocytes and rat N-acetyltransferases (Chapters II-V). These experiments facilitated the development of a dissertation project...
Oxidative stress-induced immunosuppression could be due to a decrease in CD4 + T lymphocyte activation or proliferation. 4-Hydroxynonenal (HNE), an end product of lipid peroxidation, and its protein adducts act as markers of oxidative stress. In...
The Y family of DNA polymerases in higher eukaryotes contains at least four members which are implicated in potentially error-prone replication through unrepaired damage in the genome. These proteins are encoded by the REV1, POLH, POLI, and POLK...
The leading cause of death in the United States is cardiovascular disease, a result of atherosclerosis. The reducing agent N-(2-Mercaptopropionyl)glycine (MPG) as been found to be an effective antioxidant therapy in a number of conditions, and our...
This thesis is divided into two parts below. Part I Adriamycin (ADR) can produce nephrotoxicity in rodents. The underlying mechanism may relate to ADR induced oxidative stress. In this study, we used transgenic mice (NMT3), which over-expressed the...
Diabetic cardiomyopathy (DCM) is a common complication leading to accelerated cardiovascular failure in diabetic patients. Even though the exact mechanism(s) behind this disease still remain unclear, research from several laboratories including our...
Unrepaired DNA damage poses a serious threat to the genetic stability of a replicating cell. One mechanism of tolerating this damage is translesion DNA synthesis (TLS), in which an accessory polymerase synthesizes DNA directly across from a damaged...
Copper--Physiological effect; Copper in the body; Heart--Hypertrophy
Previous studies have shown that copper (Cu) supplementation at physiologically relevant levels reverses cardiac myocyte hypertrophy induced by phenylephrine (PE), and that this effect was VEGF-dependent. Yet, the amount of VEGF in the media was...
Drug delivery systems; Curcumin--Therapeutic use--Administration
Curcumin, a plant derived compound has shown significant potency against various chronic diseases like cancer in cell culture and animal studies. However, the introduction of this compound into clinical setting is limited by its poor oral...
