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Methods Development for Toxicants Detection and Their Cellular Impacts

Abstract

Reactive oxygen species (ROS) are a class of reactive molecules that are continuously generated as a byproduct of aerobic metabolism in animals and plants. ROS were reported to play important roles in both signal transduction and homeostasis. In normal conditions, cells could maintain a delicate balance between oxidants and antioxidants. However, when ROS level go beyond its normal range, various negative effects could be induced including cytotoxicity, mutagenicity and carcinogenicity. Developing ROS detection tools and methods are of pivotal importance here to help further ROS targeted studies.

Heavy metals are another class of molecules that occur naturally with a high atomic weight. Some of them are essential nutrients that are necessary for different biological and physiological functions. Nevertheless, concerns on their health effects were raised along with their increasing usage in industry, agriculture and modern technology. Exposure to heavy metals were reported to cause carcinogen, organ damage and genotoxicity.

Regarding the molecule level mechanism of above toxicants, proteins were reported to be one of the major targets. Protein covalent modifications occur frequently in all kinds of proteins and one of the most important class is the histone protein. Post-transitional modifications (PTM) to histone, including acetylation, methylation, phosphorylation, ubiquitination etc. Other than modification types, histone modification studies are further complexed by possibilities of different modification sites. In this dissertation, Chapter 1 is an introduction on ROS, heavy metal and PTMs, as well as current analytical techniques. Chapter 2 describes a novel microgel based amplification technique aiming to study ROS. Glucose and cholesterol are also measured based on the sample technique. Chapter 3 is reporting a deep cavitand based sensing method used for histone methylation study. Chapter 4 and 5 are more in-depth studies on sensing of different PTMs with deep cavitand based sensor array. Chapter 6 describes a further application of cavitand sensor array in metal detection. In Chapter 7, future directions and some preliminary studies are described.

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